RESUMEN
AIM: The aim of this paper was to estimate the effectiveness of the contemporary oral administration of Lactobacilllus paracasei subsp paracasei F19 in association with vaginal suppositories containing Lactobacilllus acidofilus in the treatment of bacterial vaginosis and in the prevention of recurrent vaginitis. METHODS: We have recruited 60 women in good health, aged between 18 and 40 years with suspect or confirmed diagnosis of bacterial vaginosis. The women were randomized in 2 groups: Group A treated with vaginal suppositories containing Lactobacillus acidofilus (Calagin, SIFFRA, Florence); Group B treated with the same vaginal suppositories + probiotic containing Lactobacilllus paracasei subsp paracasei F 19 for oral administration (Gene-filus F19, SIFFRA, Florence). The patients were examined at the end of therapy (3 months) and then after 3 months from the end of treatment. RESULTS: In both groups at end of therapy there was a significant reduction of vaginal pH, an improvement of sniff test and of the subjective symptomatology after 3 months of treatment which still decreased during follow-up (3 months). In Group B there was a meaningful reduction of vaginal pH and of sniff test at the end of therapy and a maintenance of positive effect also after 3 months. CONCLUSIONS: The results obtained in this study show that the therapy with vaginal Lactobacillus in the treatment of bacterial vaginosis is successful. The association of oral administration is useful to balance the vaginal environment with the intestinal microflora with improvement of long-term results. The use of probiotics was determinant in the treatment of a pathology like bacterial vaginosis and as an alternative to the conventional local antibiotic therapies.
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Lactobacillus acidophilus , Lactobacillus , Fitoterapia/métodos , Vaginitis/prevención & control , Vaginosis Bacteriana/terapia , Adolescente , Adulto , Femenino , HumanosRESUMEN
OBJECTIVE: to evaluate the efficacy of combining kava extract with hormone replacement therapy in the treatment of menopausal anxiety. MATERIALS AND METHODS: HAMA score was evaluated before and after therapy in four groups of women in menopause (duration of menopause ranged from 1 to 12 years). The groups were treated with hormone replacement therapy (with and without progestogens) and kava extract or placebo for 6 months. RESULTS: A significant reduction in HAMA score was observed in all four groups of women. The reduction was more significant in groups taking kava extract than in groups on hormones only. DISCUSSION: The combined use of hormone replacement therapy and kava extract seems to be effective against menopausal anxiety. Kava extract accelerates resolution of psychological symptoms while hormone therapy safeguards against osteoporosis and cardiovascular disease.
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Ansiedad/prevención & control , Terapia de Reemplazo de Hormonas , Kava/uso terapéutico , Menopausia , Fitoterapia , Plantas Medicinales , Femenino , Humanos , Persona de Mediana Edad , Extractos Vegetales/uso terapéutico , Resultado del TratamientoRESUMEN
Allopregnanolone is a neuroactive steroid synthesized in rat gonads, adrenal cortex, and central nervous system. It has been suggested that sex steroid hormones might influence allopregnanolone concentrations but no clear data have ever been reported. The aim of the present study was to investigate the effects of administration of 17beta-estradiol (17beta-E2), the raloxifene analog LY-117018 or their combination on allopregnanolone levels in fertile and ovariectomized (OVX) rats. Thirteen groups of 12 Wistar female rats each received either 17beta-E2 (0.1 or 1 microg/day) or LY-117018 (25, 250, and 1,250 microg/day), or 17beta-E2 1 microg/day plus LY-117018: 25, 250, and 1,250 microg/day for 14 days. The rats were then sacrificed and allopregnanolone content was assessed in the hypothalamus, hippocampus, pituitary, adrenals, and serum. Ovariectomy determined a significant decrease in allopregnanolone content in the hypothalamus, hippocampus, pituitary, and serum, while increasing it in the adrenals (p<0.01). In OVX rats, the administration of either 17beta-E2 or LY- 117018 restored ovariectomy-induced allopregnanolone changes. The administration of LY-117018 in addition to 17beta-E2 to OVX animals suppressed the increase in allopregnanolone levels determined by 17beta-E2 in the hippocampus, hypothalamus, and pituitary, but not in the adrenals and serum. In fertile rats, the administration of LY-117018 reproduced the effects of ovariectomy. This study shows that the raloxifene analog LY-117018 has an estrogen-like action on the central nervous system of OVX rats when administered alone, while it acts as an antiestrogen in the presence of 17beta-E2, both in OVX animals treated with 17beta-E2 and in fertile rats. A different effect was observed in the adrenal glands. The mechanism of action of this compound has still to be clarified.
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Glándulas Suprarrenales/efectos de los fármacos , Glándulas Suprarrenales/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Estradiol/metabolismo , Antagonistas de Estrógenos/farmacología , Pregnanolona/sangre , Pirrolidinas/farmacología , Tiofenos/farmacología , Animales , Combinación de Medicamentos , Interacciones Farmacológicas/fisiología , Estradiol/farmacología , Femenino , Fertilidad/efectos de los fármacos , Fertilidad/fisiología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Ovariectomía/efectos adversos , Hipófisis/efectos de los fármacos , Hipófisis/metabolismo , Pregnanolona/biosíntesis , Clorhidrato de Raloxifeno/análogos & derivados , Ratas , Ratas WistarRESUMEN
Stress-induced neuroendocrine activities influence the regulation of endocrine glands and axes. Weight loss-related hypothalamic amenorrhea is a typical stress-induced physiopathological condition. It is characterized by increased adrenal cortex activation and by reduced GH, LH, FSH and gonadal steroid hormone levels. The aim of the present study was to investigate the effects of pivagabine, a neurotropic drug (1800 mg/day for 7 days) or placebo administration on ACTH, cortisol, GH, LH, FSH and PRL plasma levels in patients with hypothalamic amenorrhea related to weight loss. Hormonal parameters and the pulsatile release of cortisol (6-hour pulsatility, sampling every 10 minutes) were evaluated before and after 7 days of treatment. Pivagabine administration significantly reduced mean plasma ACTH (from 21.7+/-1.7 to 15.4+/-1.2 pg/ml, p<0.05) and cortisol levels (from 12.2+/-0.7 to 9.7+/-0.7 ng/ml, p<0.05) and increased GH levels (from 1.4+/-0.5 to 3.0+/-0.9 ng/ml, p<0.05). A significant reduction of cortisol pulse amplitude was observed (p<0.01) while no change in pulse frequency occurred. No changes were observed in placebo-treated subjects. LH, FSH and PRL levels were not modified by placebo or pivagabine administration. In conclusion, in patients with hypothalamic amenorrhea related to weight loss pivagabine induced a significant decrease of cortisol secretion and an increase of GH release by pivagabine administration, suggesting that this drug exerts a specific neuroendocrine modulatory role.
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Amenorrea/tratamiento farmacológico , Amenorrea/etiología , Hidrocortisona/metabolismo , Hipotálamo/fisiopatología , Estrés Fisiológico/complicaciones , Ácido gamma-Aminobutírico/análogos & derivados , Ácido gamma-Aminobutírico/uso terapéutico , Hormona Adrenocorticotrópica/sangre , Femenino , Hormona Folículo Estimulante/sangre , Hormona de Crecimiento Humana/sangre , Humanos , Hidrocortisona/sangre , Hormona Luteinizante/sangre , Periodicidad , Placebos , Prolactina/sangre , Estrés Fisiológico/fisiopatologíaRESUMEN
OBJECTIVE: Hypothalamic amenorrhea (HA) is a functional disorder caused by disturbances in gonadotropin-releasing hormone (GnRH) pulsatility. The mechanism by which stress alters GnRH release is not well known. Recently, the role of corticotropin-releasing hormone (CRH) and neurosteroids in the pathophysiology of HA has been considered. The aim of the present study was to explore further the role of the hypothalamic-pituitary-adrenal axis in HA. DESIGN: We included 8 patients (aged 23.16+/-1.72 years) suffering from hypothalamic stress-related amenorrhea with normal body weight and 8 age-matched healthy controls in the follicular phase of the menstrual cycle. METHODS: We measured basal serum levels of FSH, LH, and estradiol and evaluated ACTH, allopregnanolone and cortisol responses to CRH test in both HA patients and healthy women. RESULTS: Serum basal levels of FSH, LH, and estradiol as well as basal levels of allopregnanolone were significantly lower in HA patients than in controls (P<0.001) while basal ACTH and cortisol levels were significantly higher in amenorrheic patients with respect to controls (P<0.001). The response (area under the curve) of ACTH, allopregnanolone and cortisol to CRH was significantly lower in amenorrheic women compared with controls (P<0.001, P<0.05, P<0.05 respectively). CONCLUSIONS: In conclusion, women with HA, despite the high ACTH and cortisol levels and, therefore, hypothalamus-pituitary-adrenal axis hyperactivity, are characterized by low allopregnanolone basal levels, deriving from an impairment of both adrenal and ovarian synthesis. The blunted ACTH, allopregnanolone and cortisol responses to CRH indicate that, in hypothalamic amenorrhea, there is a reduced sensitivity and expression of CRH receptor. These results open new perspectives on the role of neurosteroids in the pathogenesis of hypothalamic amenorrhea.
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Hormona Adrenocorticotrópica/sangre , Amenorrea/etiología , Amenorrea/metabolismo , Hormona Liberadora de Gonadotropina/metabolismo , Hidrocortisona/sangre , Hipotálamo/metabolismo , Pregnanolona/sangre , Adulto , Amenorrea/sangre , Peso Corporal , Estudios de Casos y Controles , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Fase Folicular/sangre , Humanos , Sistema Hipotálamo-Hipofisario/metabolismo , Hormona Luteinizante/sangre , Sistema Hipófiso-Suprarrenal/metabolismo , Factores de TiempoRESUMEN
Raloxifene is a selective estrogen receptor modulator with a benzothiophene structure, that exerts an estrogen-like action on some target tissues and an anti-estrogenic action on the uterus and breasts. A limited number of data are available on the effect of raloxifene on neuroendocrine function. Since beta-endorphin (beta-EP) is considered a marker of neuroendocrine function, the aim of the present study was to evaluate the effects of a 14 day treatment with a raloxifene analog, LY 117018, on beta-EP content in the hypothalamus, hippocampus, anterior and neuro-intermediate pituitary lobe, and in the plasma of fertile and ovariectomized (ovx) rats. The effect of LY 117018 in ovx rats was compared to that of 17 beta-estradiol. beta-EP contents were measured by a specific radioimmunoassay. While ovariectomy determined a significant decrease in beta-EP levels in the anterior and neurointermediate pituitary lobe and plasma (p < 0.01), no changes of beta-EP content in the hypothalamus and hippocampus were found. The administration of 17 beta-estradiol or LY 117018 in ovx rats significantly increased beta-EP concentration in the anterior and neurointermediate pituitary lobe, in the hypothalamus and plasma (p < 0.01), though they did not significantly modify hippocampal beta-EP content. When LY 117018 was administered together with 17 beta-estradiol in ovx animals, a clear anti-estrogenic effect in all organs and in plasma was observed, resulting in significantly lower beta-EP content with respect to the group treated with 17 beta-estradiol alone (p < 0.01). The chronic administration of LY 117018 in fertile rats significantly decreased beta-EP content in the anterior pituitary, hippocampus and plasma (p < 0.01), while it increased beta-EP hypothalamic content and did not change beta-EP content in the neurointermediate lobe. In conclusion, raloxifene analog LY 117018 has an estrogen-like action on neuroendocrine opiatergic pathways when administered alone in ovx rats, while it exerts an anti-estrogen effect in fertile or in ovx rats treated with 17 beta-estradiol.
Asunto(s)
Antagonistas de Estrógenos/farmacología , Sistema Nervioso/efectos de los fármacos , Pirrolidinas/farmacología , Clorhidrato de Raloxifeno/análogos & derivados , Tiofenos/farmacología , Animales , Estradiol/farmacología , Femenino , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Sistema Nervioso/metabolismo , Ovariectomía , Adenohipófisis/efectos de los fármacos , Adenohipófisis/metabolismo , Neurohipófisis/efectos de los fármacos , Neurohipófisis/metabolismo , Ratas , Ratas Wistar , betaendorfina/sangre , betaendorfina/metabolismoRESUMEN
The objective of the present study was prospectively and randomly to evaluate the role of L-arginine in improving uterine and follicular Doppler flow and in improving ovarian response to gonadotrophin in poor responder women. A total of 34 patients undergoing assisted reproduction was divided in two groups according to different ovarian stimulation protocols: (i) flare-up gonadotrophin-releasing hormone analogue (GnRHa) plus elevated pure follicle stimulating hormone (pFSH) (n = 17); and (ii) flare-up GnRHa plus elevated pFSH plus oral L-arginine (n = 17). During the ovarian stimulation regimen, the patients were submitted to hormonal (oestradiol and growth hormone), ultrasonographic (follicular number and diameter, endometrial thickness) and Doppler (uterine and perifollicular arteries) evaluations. Furthermore, the plasma and follicular fluid concentrations of arginine, citrulline, nitrite/nitrate (NO2-/NO3-), and insulin-like growth factor-1 (IGF-1) were assayed. All 34 patients completed the study. In the L-arginine treated group a lower cancellation rate, an increased number of oocytes collected, and embryos transferred were observed. In the same group, increased plasma and follicular fluid concentrations of arginine, citrulline, NO2-/NO3-, and IGF-1 was observed. Significant Doppler flow improvement was obtained in the L-arginine supplemented group. Three pregnancies were registered in these patients. No pregnancies were observed in the other group. It was concluded that oral L-arginine supplementation in poor responder patients may improve ovarian response, endometrial receptivity and pregnancy rate.
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Arginina/uso terapéutico , Fertilización In Vitro/métodos , Inducción de la Ovulación/métodos , Adulto , Arginina/administración & dosificación , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Gonadotropina Coriónica/administración & dosificación , Estradiol/sangre , Femenino , Fármacos para la Fertilidad Femenina/administración & dosificación , Hormona Folículo Estimulante/administración & dosificación , Hormona de Crecimiento Humana/sangre , Humanos , Infertilidad Femenina/tratamiento farmacológico , Infertilidad Femenina/fisiopatología , Infertilidad Femenina/terapia , Leuprolida/administración & dosificación , Ovario/irrigación sanguínea , Ovario/diagnóstico por imagen , Ovario/efectos de los fármacos , Embarazo , Estudios Prospectivos , UltrasonografíaRESUMEN
Aging in women and men is characterized by a progressive decline of circulating dehydroepiandrosterone (DHEA) levels and its sulfate ester (DHEAS). The improvement of wellbeing described in postmenopausal women treated with DHEA suggests that this steroid may exert specific actions on the central nervous system (CNS). The postmenopausal period is associated with several neuroendocrine modifications. The decrease of circulating levels of beta-endorphin is considered a hormonal marker of those changes. The aim of the present study was to investigate neuroendocrine and behavioral effects of three months of DHEAS supplementation in postmenopausal women. Postmenopausal women (n = 22) were divided in three groups: the first group was treated with oral DHEAS (n = 8) (50 mg/day), the second treated with the same dose of oral DHEAS + transdermal estradiol (n = 8) (DHEAS) 50 mg/day, estradiol 50 micrograms/patch) and the third with transdermal estradiol alone (n = 6) (50 micrograms/day). Before and after 1, 2 and 3 months of therapy, the following circulating steroid and protein hormone levels were evaluated: DHEA, DHEAS, androstenedione, testosterone, estrone, estradiol, 17-hydroxyprogesterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), beta-endorphin, growth hormone (GH) and cortisol, and a Kupperman score was performed. Before and after treatments, plasma beta-endorphin levels were evaluated in response to three neuroendocrine tests: (a) clonidine, an alpha 2-presynaptic adrenergic agonist (1.25 mg i.v.) (b) naloxone, an opioid receptor antagonist (4 mg i.v.) and (c) fluoxetine, a serotonin selective reuptake inhibitor (30 mg p.o.). In both groups of women treated with DHEAS, mean basal serum DHEA, DHEAS, androstenedione, and testosterone levels significantly increased after treatment, while no changes were shown in the group receiving estradiol alone. Serum estradiol, estrone, GH and plasma beta-endorphin levels significantly increased progressively for the three months of treatment, with higher levels for estrone and estradiol in subjects receiving estradiol alone or plus DHEAS. Serum SHBG, cortisol, and 17-hydroxyprogesterone did not show significant variations under any treatment. Serum LH and FSH levels showed a significant decrease in groups treated with estradiol alone or plus DHEAS at the second and third months. The Kupperman score showed that all treatments were associated with similar and progressive improvement. Before therapy clonidine, naloxone and fluoxetine stimuli failed to modify circulating beta-endorphin levels. After each of the treatments, the beta-endorphin response was completely restored and was similar, independent of the kind of therapy. Restoration of the beta-endorphin response to specific stimuli suggests that DHEAS and/or its active metabolites modulates the neuroendocrine control of pituitary beta-endorphin secretion, which may support the therapeutic efficacy of the DHEAS on behavioral symptoms.
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Deshidroepiandrosterona/farmacología , Estradiol/farmacología , betaendorfina/biosíntesis , Administración Oral , Antagonistas Adrenérgicos alfa/farmacología , Androstenodiona/sangre , Área Bajo la Curva , Climaterio/fisiología , Clonidina/farmacología , Deshidroepiandrosterona/sangre , Deshidroepiandrosterona/uso terapéutico , Estradiol/sangre , Estradiol/uso terapéutico , Estrona/sangre , Femenino , Fluoxetina/farmacología , Humanos , Persona de Mediana Edad , Análisis Multivariante , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Estudios Prospectivos , Radioinmunoensayo , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Somatostatina/sangre , Testosterona/sangre , betaendorfina/sangreRESUMEN
Severe dieting and negative energy balance usually lead to the occurrence of amenorrhea together with several endocrine disturbances such as the "low T3 syndrome" and an abnormal GH secretion. To evaluate whether estrogen replacement therapy (ERT) affects thyroid hormones and GH secretion, two groups of patients affected by weight-loss-related amenorrhea and with low plasma T3 levels were treated with two different schedules of ERT using 50 or 100 micrograms estradiol transdermal patches twice a week (Dermestril, Rottapharm, Monza, Italy). Before and after 5 weeks of therapy in each patient thyroid hormones, spontaneous GH secretion and GH-RH-induced GH release were evaluated. After ERT, plasma GH and IGF-1 levels increased in both groups and a consistent change in GH spontaneous release was observed. Conversely the low T3 plasma levels and GH-RH-induced GH response were not modified by ERT. Our present data suggest that in amenorrhea related to weight-loss, hormonal abnormalities are only in part dependent from the hypoestrogenic condition.
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Amenorrea/fisiopatología , Terapia de Reemplazo de Estrógeno , Hormona Liberadora de Hormona del Crecimiento/farmacología , Hormona de Crecimiento Humana/metabolismo , Triyodotironina/deficiencia , Administración Cutánea , Adulto , Amenorrea/etiología , Índice de Masa Corporal , Estradiol/administración & dosificación , Estradiol/uso terapéutico , Femenino , Humanos , Hipotálamo/fisiopatología , Periodicidad , Pérdida de PesoRESUMEN
The central nervous system (CNS) is able to synthesize and/or metabolize steroid hormones. These neuroactive steroids are capable of modulating several brain functions and, among these, they seem to regulate the hypothalamic-pituitary-gonadal (HPG) axis. Indeed, recent observations have shown that 5 alpha-pregnane-3 alpha-ol-20-one (allopregnanolone), one of the most abundant naturally occurring neuroactive steroids, suppresses ovulation and sexual behaviour when administered within the CNS. The present study was undertaken to evaluate the effects of allopregnanolone and its inactive stereoisomer, 5 alpha-pregnane-3 beta-ol-20-one, upon the release of gonadotropin-releasing hormone (GnRH) from individually-incubated hemihypothalami. Allopregnanolone suppressed GnRH release in a concentration-dependent manner with maximal activity in the nanomolar range, a range at which this neurosteroid is capable of playing a biological action. The specificity of allopregnanolone suppression of GnRH release was provided by the lack of effect of its known inactive stereoisomer. To evaluate the involvement of gamma-aminobutyric acidA (GABAA) receptor, we examined the effects of two neurosteroids with GABA-antagonistic properties, pregnanolone sulfate (PREG-S) and dehydroepiandrosterone sulfate (DHEAS), and of bicuculline, a selective antagonist of the GABA binding site on the GABAA receptor, on allopregnanolone (10 nM)-suppressed GnRH release. Both PREG-S and bicuculline overcame the inhibitory effects of allopregnanolone on GnRH release, whereas DHEAS did not. To substantiate the involvement of the GABAA receptor further, we tested the effects of muscimol, a selective agonist for this receptor, which suppressed GnRH release. In conclusion, allopregnanolone suppressed hypothalamic GnRH release in vitro and this effect appeared to be mediated by an interaction with the GABAA receptor. We speculate that the inhibitory effect of allopregnanolone on the HPG axis may also be caused by its ability to suppress hypothalamic GnRH release.
Asunto(s)
Moduladores del GABA/farmacología , Hormona Liberadora de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Pregnanolona/farmacología , Receptores de GABA-A/metabolismo , Animales , Sulfato de Deshidroepiandrosterona/farmacología , Depresión Química , Antagonistas del GABA/farmacología , Hipotálamo/efectos de los fármacos , Isomerismo , Masculino , Técnicas de Cultivo de Órganos , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVES: A progressive decline of plasma dehydroepiandrosterone (DHEA) levels occurs in women during aging related to the reduction of adrenocortical secretion. A specific action of DHEA on the central nervous system (CNS) is suggested by the improvement of psychological and physical well-being in postmenopausal women after DHEA supplementation. The aim of the present study was to investigate the neuroendocrine effects of short-term DHEA supplementation in postmenopausal women, evaluating changes of plasma beta-endorphin (beta-EP) and growth hormone (GH) before and after oral DHEA (100 mg/day) for 7 days in postmenopausal women (n = 6). METHODS: Before and after 7 days of DHEA supplementation, postmenopausal women underwent a neuroendocrine test with clonidine, an alpha 2 presinaptic agonist for adrenergic system (1.25 mg i.v.). Basal plasma DHEA, androstenedione (A), testosterone (T), estrone (E1) and estradiol (E2) levels were evaluated before and after treatment, while plasma beta-EP and GH levels were measured before and 15, 30, 45, 60 and 90 min after clonidine injection. RESULTS: Basal plasma beta-EP and GH levels did not show a significant difference before and after short-term DHEA administration, while circulating A, T, E1 and E2 significantly increased after treatment. The clonidine test induced a significant increase of plasma beta-EP levels in women after receiving DHEA supplementation but not before; conversely, plasma GM levels increased both before and after treatment. CONCLUSIONS: The present study indicates that short-term DHEA supplementation in postmenopausal women is able to restore the impaired response of pituitary beta-EP to clonidine, an alpha 2 presinaptic agonist. According to these data it is possible to hypothesize that DHEA could play a role in the psychological and physical well-being of postmenopausal women acting via a restoration of neuroendocrine control of antero-pituitary beta-EP secretion.
Asunto(s)
Deshidroepiandrosterona/farmacología , Hormona de Crecimiento Humana/efectos de los fármacos , Sistemas Neurosecretores/efectos de los fármacos , Posmenopausia/efectos de los fármacos , betaendorfina/efectos de los fármacos , Administración Oral , Androstenodiona/sangre , Androstenodiona/metabolismo , Clonidina , Deshidroepiandrosterona/administración & dosificación , Deshidroepiandrosterona/sangre , Deshidroepiandrosterona/metabolismo , Estrona/sangre , Estrona/metabolismo , Femenino , Hormona de Crecimiento Humana/sangre , Hormona de Crecimiento Humana/metabolismo , Humanos , Persona de Mediana Edad , Sistemas Neurosecretores/metabolismo , Posmenopausia/sangre , Simpaticolíticos , Testosterona/sangre , Testosterona/metabolismo , betaendorfina/sangre , betaendorfina/metabolismoRESUMEN
OBJECTIVE: Allopregnanolone is a potent neuroactive steroid hormone produced in the brain and in peripheral endocrine glands. The present study investigated possible age-related variations in allopregnanolone content in brain areas, endocrine glands and serum of male rats. DESIGN: Wistar male rats were categorized into 5 groups (6 rats in each) according to age: 6, 12, 16, 18 and 20 months respectively. METHODS: Allopregnanolone content in acidic homogenates of brain cortex, hypothalamus, pituitary, adrenals and gonads was measured by a specific radioimmunoassay. Serum allopregnanolone, corticosterone and testosterone were also assayed by radioimmunoassay. RESULTS: Brain cortex allopregnanolone content decreased significantly with age, while hypothalamic allopregnanolone content remained constant until 18 months and increased significantly at 20 months. Pituitary content showed a significant age-related reduction. Adrenal allopregnanolone content remained constant until 18 months, and was significantly higher at 20 months. Testis and serum allopregnanolone contents showed significant age-related increases. Serum testosterone levels showed an age-related decrease, while no age-related variation in serum corticosterone was found. CONCLUSIONS: The present study showed a significant impact of aging on allopregnanolone contents in brain, endocrine glands and serum, showing an age-related decrease in brain cortex and pituitary, and an age-related increase in testes, adrenals and serum.
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Envejecimiento/fisiología , Química Encefálica/fisiología , Glándulas Endocrinas/química , Pregnanolona/análisis , Testículo/química , Glándulas Suprarrenales/química , Envejecimiento/sangre , Animales , Corteza Cerebral/química , Estudios de Cohortes , Corticosterona/sangre , Reacciones Cruzadas , Hipotálamo/química , Sueros Inmunes/inmunología , Masculino , Hipófisis/química , Pregnanolona/sangre , Radioinmunoensayo , Ratas , Ratas Wistar , Ovinos , Testosterona/sangreRESUMEN
OBJECTIVE: Since hormonal replacement therapy (HRT) affects plasma GH levels, the present study aimed to verify the effect of tibolone, a synthetic steroid, on modulating spontaneous and growth hormone releasing hormone (GH-RH) induced GH secretion. METHODS: Postmenopausal women (n = 30) were enrolled and randomly subdivided in three groups (n = 10 each group): (1) treated with transdermal estradiol (50 micrograms) (Dermestrill, Rottapharm, Monza, Italy) biweekly; (2) treated with transdermal estradiol (100 micrograms) (Dermestrill, Rottapharm, Monza, Italy) biweekly; (3) treated with tibolone 2.5 mg/day (Livial, Organon Italia, Rome, Italy). Patients underwent a GH-RH test (1 microgram/kg) and 15 of them underwent to a pulsatility study before and 5 weeks after treatment. RESULTS: Mean (+ S.E.M.) GH plasma levels increased in all patients after any type of HRT. GH response to GH-RH stimulation (expressed as maximal response to GH-RH or as delta value) was similar in the three groups while significant changes occurred in spontaneous pulsatile GH release. Tibolone and both dosages of transdermal estradiol significantly reduced GH pulse frequency and increased pulse amplitude. CONCLUSIONS: The reduced plasma GH levels observed during postmenopause are probably related to a reduced endogenous GH-RH and not to a reduced pituitary ability to respond to GH-RH. In addition tibolone, as well as transdermal estradiol, are effective in restoring the spontaneous GH episodic release.
Asunto(s)
Anabolizantes/administración & dosificación , Estradiol/administración & dosificación , Terapia de Reemplazo de Estrógeno/efectos adversos , Hormona Liberadora de Hormona del Crecimiento/administración & dosificación , Hormona de Crecimiento Humana/metabolismo , Norpregnenos/administración & dosificación , Posmenopausia/sangre , Administración Cutánea , Índice de Masa Corporal , Relación Dosis-Respuesta a Droga , Terapia de Reemplazo de Estrógeno/métodos , Femenino , Hormona Folículo Estimulante/sangre , Hormona de Crecimiento Humana/efectos de los fármacos , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Hormona Luteinizante/sangre , Posmenopausia/efectos de los fármacosRESUMEN
OBJECTIVE: To evaluate the GH-releasing hormone (GH-RH)-induced response of GH in patients affected by hypothalamic amenorrhea. DESIGN: Patients affected by weight-loss-related hypothalamic amenorrhea (n = 28) were studied and compared with 20 healthy controls. Among patients with weight-loss amenorrhea, both hypogonadotropic and normogonadotropic conditions were present. All subjects underwent a GH-RH test (GEREF, Sereno, Rome, Italy) (1 microgram/kg body weight IV). Plasma GH concentrations were determined using commercially available RIAs. Also, in selected samples insulin-like growth factor-I (IGF-I) levels were measured. RESULTS: Basal plasma IGF-I levels as well as body mass index (BMI) were lower in amenorrheic patients than in healthy controls. No significant correlation was found between BMI and IGF-I or E2 plasma levels or between LH and IGF-I plasma levels. The basal GH plasma levels were comparable in all groups of subjects. The GH-RH--induced GH response evaluated as maximal release and as area under the curve (AUC) was higher in amenorrheic patients than in control subjects. CONCLUSIONS: The amenorrheic condition associated with reduced BMI changes the GH-RH--induced GH response in hypothalamic amenorrhea, supporting a GH and a IGF-I disregulation in weight-loss--related amenorrhea.
Asunto(s)
Amenorrea/fisiopatología , Hormona del Crecimiento/sangre , Enfermedades Hipotalámicas/complicaciones , Sermorelina , Pérdida de Peso , Amenorrea/etiología , Índice de Masa Corporal , Estradiol/sangre , Femenino , Humanos , Hipotálamo/fisiopatología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Hormona Luteinizante/sangreRESUMEN
Because endogenous opioids have been considered to be deeply involved as a causal factor of hypothalamic amenorrhoea, this study was designed to evaluate the efficacy of the administration of naltrexone, an antagonist of opioid receptors, on luteinizing hormone (LH) secretion in patients with hypothalamic amenorrhoea. A total of 30 patients with hypothalamic amenorrhoea were studied. Patients were divided into two groups: group A, hypogonadotrophic (n = 15), and group B, normogonadotrophic (n = 15). All patients were administered naltrexone at a dose of 50 mg/ day per os for 6 months. A third group of 10 amenorrhoeic patients was treated with placebo per os with the same schedule. All patients were evaluated for LH spontaneous pulsatile release in baseline conditions and after 3 and 6 months of treatment. Plasma gonadal steroid concentrations increased significantly in all patients after 3 months of naltrexone therapy, but only hypogonadotrophic patients showed a sharp increase in both LH plasma concentrations and LH pulse amplitude within the first 3 months of treatment which remained unchanged until the sixth month of treatment. Plasma follicle stimulating hormone concentrations did not change significantly in any patient. Menstrual bleeding occurred within 90 days of the beginning of treatment in 24 out of the 30 patients. Patients treated with placebo did not show a significant change in gonadotrophin and gonadal steroid plasma concentrations. The results of our study support the efficacy of naltrexone administration on neuroendocrine pathways controlling LH secretion in patients with hypothalamic amenorrhoea.
Asunto(s)
Amenorrea/tratamiento farmacológico , Amenorrea/fisiopatología , Hipotálamo/efectos de los fármacos , Hipotálamo/fisiopatología , Hormona Luteinizante/metabolismo , Naltrexona/uso terapéutico , Sistemas Neurosecretores/efectos de los fármacos , Sistemas Neurosecretores/fisiopatología , Femenino , Hormona Folículo Estimulante/metabolismo , Humanos , Naltrexona/administración & dosificación , Antagonistas de NarcóticosRESUMEN
The present study investigated the effect of allopregnanolone (5 alpha-pregnan-3 alpha-ol-20-one) or of passive immunoneutralization of brain allopregnanolone, the most potent steroid produced by neurons, on ovulation rate and sexual behavior in female rats. Allopregnanolone was injected intracerebroventricularly in rats on diestrus and proestrus and tests were done on estrus. The intracerebroventricular injection of allopregnanolone significantly decreased the number of oocytes collected on estrus (p < 0.01). To support a physiological involvement, antiserum to allopregnanolone was injected centrally to block the activity of the endogenous neurosteroid. When administered on diestrus and proestrus or only on proestrus, the antiserum was shown to be correlated with a significant increase (p < 0.01) in oocytes retrieved on estrus. In female rats treated with antiserum to allopregnanolone, the lordosis intensity was augmented significantly as compared to controls. Finally, the possible changes of medial basal hypothalamus concentration of allopregnanolone throughout the estrous cycle and at the time of ovulation were investigated. Hypothalamic extracts were eluted on high-pressure liquid chromatography and allopregnanolone concentration was measured by radioimmunoassay. Brain cortex was used as control tissue. Hypothalamic allopregnanolone concentration on proestrus morning and afternoon was found to be significantly lower than in the remaining phases of the estrous cycle (p < 0.01), while no significant changes were observed in brain cortex concentration of allopregnanolone. The present results suggest that hypothalamic allopregnanolone may be involved in the mechanism of ovulation, affecting hormonal and behavioral events.
Asunto(s)
Pregnanolona/fisiología , Reproducción/fisiología , Animales , Encéfalo/metabolismo , Diestro , Estro , Femenino , Hipotálamo/metabolismo , Inmunización Pasiva , Inyecciones Intraventriculares , Oocitos/efectos de los fármacos , Ovulación/efectos de los fármacos , Postura , Pregnanolona/inmunología , Pregnanolona/farmacología , Proestro , Ratas , Conducta Sexual Animal/efectos de los fármacosRESUMEN
OBJECTIVE: To evaluate pituitary-adrenal responsive to corticotropin-releasing hormone (CRH) stimulus in polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. PATIENTS: Twelve women aged 17 to 32 years, who had been diagnosed as having PCOS, were studied. Fifteen appropriately age- and weight-matched ovulatory patients served as the control. INTERVENTION: In the early follicular phase or after progestin-induced menses, human CRH was injected at 8:00 A.M. and blood samples were collected at 0, 15, 30, 60, and 90 minutes after stimulus. Plasma levels of ACTH and cortisol were measured. RESULTS: Baseline levels of ACTH and cortisol were similar in PCOS and control patients. Both ACTH and cortisol response to CRH were markedly greater in the PCOS population as compared with controls. Moreover, ACTH- and cortisol-stimulated secretion was prolonged for the whole period of the study in hyperandrogenic patients with respect to controls, where baseline levels were attained 60 minutes after the stimulus. CONCLUSIONS: Our results are consistent with the hypothesis that women with PCOS may demonstrate hyperfunction of the hypothalamic-pituitary-adrenal axis, which may be involved in the physiopathologic events leading to the complexity of the syndrome.
Asunto(s)
Hormona Adrenocorticotrópica/sangre , Hormona Liberadora de Corticotropina , Hidrocortisona/sangre , Síndrome del Ovario Poliquístico/fisiopatología , Adolescente , Glándulas Suprarrenales/fisiopatología , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Hipotálamo/fisiopatología , Cinética , Hipófisis/fisiopatología , Síndrome del Ovario Poliquístico/sangreRESUMEN
The availability of the most selective, high-affinity, natural opioid agonists for mu-receptors (dermorphin-DM) and delta-receptors (deltorphin-DT) has provided the possibility for in vivo studying of the role of acute and chronic activation of mu- and delta-opioid receptors on the functional activity of the hypothalamus-pituitary-adrenocortical (HPA) axis, both in basal conditions and in response to an acute stress in adult male rats. Plasma corticosterone (CS) and beta-endorphin-like-immunoreactivity (beta-EP-LI) levels were measured by specific radioimmunoassays before and after 5 and 30 minutes from the exposure to cold (3 +/- 0.5 C) water and forcing them to swim for 10 minutes (acute cold swimming stress). Acute administration of DM, the specific mu-receptor agonist, enhanced basal and stress induced plasma levels of CS and beta-EP-LI. These effects were antagonized by pretreatment with naloxone, specific mu-opioid receptor antagonist, but not by naltrindole, a delta-opioid receptor antagonist. Long-term administration of DM did not alter resting plasma levels of CS and beta-EP-LI, but significantly reduced stress-induced increase of these hormones. Both the acute and chronic administration of the DT, highly selective delta-opioid receptors agonist, failed to modify resting and stress induced hormone levels. Our present data show that DM throughout mu-opioid receptors, but not DT, modulates the response of HPA axis to acute stress in rats, increasing or decreasing the release of CS and beta-EP-LI when acutely or chronically administered, respectively.
Asunto(s)
Glándulas Suprarrenales/fisiopatología , Hipófisis/fisiopatología , Receptores Opioides mu/fisiología , Estrés Fisiológico/fisiopatología , Secuencia de Aminoácidos , Animales , Frío , Corticosterona/sangre , Hipotálamo/fisiopatología , Masculino , Datos de Secuencia Molecular , Naloxona/farmacología , Oligopéptidos/farmacología , Péptidos Opioides , Ratas , Ratas Sprague-Dawley , Receptores Opioides delta/fisiología , Natación , betaendorfina/sangreRESUMEN
Chronic stress affects the reproductive function by modifying the neuroendocrine homeostasis. The aim of the present study was to clarify the neuroendocrine and the gonadal changes following chronic intermittent stress in male rats and the action of a neuroactive drug, acetyl-l-carnitine (ALC). The effect of two different stressors, cold water swimming or ether, on central beta-endorphin (beta-EP) and GnRH contents, and on plasma testosterone levels was investigated. In addition, the response to an acute stress in chronically stressed rats, treated or untreated with ALC (10 mg/day/rat p.o.), was evaluated. The stressors were applied twice a day for 10 days, and rats were killed before, during and after the last stress session. Mediobasal hypothalamus (MBH) beta-EP and GnRH contents, and plasma testosterone levels were evaluated by radioimmunoassay. The following results were obtained: (1) both chronic swimming and ether stress caused a decrease in hypothalamic beta-EP contents; (2) MBH GnRH contents increased after chronic swimming stress but not after ether stress; (3) chronic swimming stress induced a twofold decrease in plasma testosterone levels, while no changes were observed after ether stress; (4) the treatment with ALC prevented the decrease in plasma testosterone levels after chronic swimming stress, and (5) acute stress in chronically stressed animals caused an increase in MBH-beta-EP. The present data showed that chronic swimming stress reduces the reproductive capacity and impairs the capacity to respond to the acute stress and that ALC modulates the hormonal changes to physical stress and prevents the antireproductive effect of chronic cold swimming.
Asunto(s)
Acetilcarnitina/farmacología , Hormona Liberadora de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Estrés Fisiológico/metabolismo , Testosterona/sangre , betaendorfina/metabolismo , Animales , Enfermedad Crónica , Éter/toxicidad , Hipotálamo/efectos de los fármacos , Hipotálamo/fisiología , Masculino , Radioinmunoensayo , Ratas , Ratas Wistar , Estrés Fisiológico/inducido químicamente , NataciónRESUMEN
Immunological, neuroendocrine and psychological parameters were examined in 14 psychophysically healthy subjects and in 17 panic disorder patients before and after a 30-day course of alprazolam therapy. T lymphocyte proliferation in response to the mitogen phytohemagglutinin, lymphocyte beta-endorphin (beta-EP) concentrations, plasma ACTH, cortisol and beta-EP levels were examined in basal conditions and after corticotropin-releasing hormone (CRH) stimulation. Cortisol inhibition by dexamethasone (DST) and basal growth hormone (GH) and prolactin levels were also examined. Depression, state or trait anxiety, anticipatory anxiety, agoraphobia, simple and social phobias, severity and frequency of panic attacks were monitored by rating scales. The immune study did not reveal any significant difference between patients and controls, or any effect of alprazolam therapy. The hormonal data for the two groups were similar, except for higher than normal basal ACTH and GH plasma levels, lower than normal ratios between the ACTH and cortisol responses to CRH, and blunted DST in some patients. All the impairments improved after alprazolam therapy, in parallel with decreases in anxiety and in severity and frequency of panic attacks.