Hormonal and Histomorphologic Effects of Azadirachta indica leaf Extract on the Pars Anterior of Wistar Rats / Efectos Hormonales e Histomorfológicosdel Extracto de la Hoja de Azadirachta indica en la Pars Anterior de Ratas Wistar

Azadirachta indica is a tree whose medicinal value is unquantifiable. Any part of the tree can be used in the treatment of malarial infection. Reports have indicated its antifertility effects, and this necessitated this study on the effects of the methanol leaf extract on serum luteinizing (LH) and follicle stimulating hormones (FSH) levels and the histomorphology of the pars anterior of Wistar rats. Thirty adult male Wistar rats were equally divided into 3 groups of A, B and C. Group A was the control and the animals received distilled water orally, while groups B and C were treated with 200mg/kg and 400mg/kg respectively of the leaf extract by oral gavage for fourteen days. On day fifteen, the animals were sacrificed by chloroform anaesthesia. Blood was obtained from their hearts, while the skull was opened to assess the hypophysis. Hormonal assay showed that luteinizing (LH) and follicle stimulating (FSH) hormone levels in the serum were lower in groups B and C treated with 200mg/kg and 400mg/kg respectively of the leaf extract, while that of LH were significant (P<0.001). Histomorphologic sections of the pars anterior revealed reduced acidophil and basophil populations, with prominent degranulated chromophobes which were larger in the group treated with 400mg/kg of A. indica leaf extract. This group also presented hypertrophy of the basophils compared to the control. In conclusion, methanol leaf extract of A. indica decreases serum LH and FSH and caused histomorphologic changes in the pars anterior of adult male Wistar rats.

Azadirachta indica es un árbol cuyo valor medicinal es invaluable. Cualquier parte del árbol se puede utilizar en el tratamiento de la infección por malaria. Reportes han indicado su efecto antifertilidad, lo que requirió estudiar los efectos del extracto metanólico de la hoja sobre los niveles séricos de las hormonas luteinizante (LH) y folículo estimulante (FSH) y la histomorfología de la pars anterior de ratas Wistar. Treinta ratas Wistar adultas fueron divididas en tres grupos. El grupo A fue utilizado como control y los animales recibieron agua destilada por vía oral, mientras que los grupos B y C fueron tratados con 200 mg/kg y 400 mg/kg respectivamente, con extracto de hoja mediante una sonda nasogástrica durante catorce días. A los quince días, los animales fueron sacrificados por anestesia con cloroformo. Se obtuvo sangre desde sus corazones, mientras que el cráneo fue abierto para evaluar la hipófisis. Los ensayos hormonales mostraron que los niveles en suero de la LH y FSH se redujeron en los grupos B y C, tratados con 200 mg/kg y 400 mg/kg respectivamente, siendo la reducción de LH significativa (p<0,001). Secciones histomorfológicos de la pars anterior revelaron una reducción de las poblaciones acidófilas y basófilas, con prominentes cromófobos degranulados que fueron mayores en el grupo tratado con 400 mg/kg del extracto de A. indica. Este grupo también presentó hipertrofia de los basófilos en comparación con el control. En conclusión, el extracto alcohólico de la hoja de de A. indica disminuye el nivel sérico de LH y FSH y provoca cambios histomorfológicos en la pars anterior de ratas Wistar adultas.

Luteinizing hormone reduction by the male potency herb, Butea superba Roxb.

To determine if Butea superba Roxb., a traditional Thai male potency herb, has androgenic activity in 60-day-old male Wistar rats, we measured its effects on the pituitary-testicular axis and sex organs. Intact and orchidectomized adult male rats were subdivided into five groups (10 rats/group): distilled water, Butea superba (BS)-10, BS-50, BS-250, and testosterone propionate (TP). They received 0, 10, 50, and 250 mg·kg body weight-1·day-1 BS in distilled water by gavage and 6 mg·kg body weight-1·day-1 TP sc, respectively, during the 30-day treatment period. Blood was collected every 15 days and luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone were measured. Changes of weight and histological appearance of sex organs were determined at the end of the 30-day treatment and 15-day post-treatment periods. TP treatment reduced serum FSH and LH levels and significantly increased the weight of the seminal vesicles and epididymis, in accordance with histopathological changes, in both intact and orchidectomized rats. No changes in serum testosterone, LH, and FSH levels were observed in any of the intact rats treated with BS, but a significant increase in seminal vesicle weight was observed only in the BS-250 group. Although a significant reduction in serum LH was detected in the BS-50 and BS-250 groups of orchidectomized rats, no significant change in weight or histology of sex organs was observed. Thus, we conclude that B. superba needs endogenous testosterone to work synergistically to stimulate the accessory sex organ of intact animals and can potentially exhibit an LH reduction effect in orchidectomized animals.

Effect of saffron [Crocus sativus] extract on level of FSH, LH and testosterone in mice

Saffron is widely used as a food flavor and has well known medicinal effects. Recent studies have revealed that main components of saffron including carotenoids: crocin, crocetin, picrocrocin and safranal have a large number of physiological effects on different biological systems. We decided to assess the possible effect of saffron extract on concentratians of LH, FSH and testosterone in mice. Four groups each including eight adult male Balb/C mice weighing 30 5g were chosen. Normal saline was administered as placebo to control group and saffron extract in doses of 25 mg kg / 48h, 50mg kg / 48h and 100mg kg / 48h was injected intraperitoneally for 20 days to test groups. Serum FSH, LH and testosterone, were measured using ELISA. The level of FSH, LH and testosterone significantly increased in 100mg kg saffron treated group, as compared with with placebo group. No significant differences were observed between other test groups and placebo. The study indicates efficacy of saffron extract in dose of 100 mg/kg/ 48h on pituitary-testis axis in mice. However further studies are needed to determine the effect of saffron on human reproductivity

Prenatal testosterone treatment alters LH and testosterone responsiveness to GnRH agonist in male sheep

Although evidence is accumulating that prenatal testosterone (T) compromises reproductive function in the female, the effects of excess T in utero on the postnatal development of male reproductive function has not been studied. The aim of this study was to assess the influence of prenatal T excess on age-related changes in pituitary and gonadal responsiveness to GnRH in the male sheep. We used the GnRH agonist, leuprolide (10 µg/kg), as a pharmacologic challenge at 5, 10, 20 and 30 weeks of age. These time points correspond to early and late juvenile periods and the prepubertal and postpubertal periods of sexual development, respectively. LH and T were measured in blood samples collected before and after GnRH agonist administration. The area under the response curve (AUC) of LH increased progressively in both controls and prenatal T-treated males from 5 to 20 weeks of age (P<0.01). The LH responses in prenatal T-treated males were lower at 20 and 30 weeks of age compared to controls (P<0.05). AUC-T increased progressively in control males from 5 through 30 weeks of age and prenatal T-treated males from 5 to 20 weeks of age. The T response in prenatal T-treated males was higher at 20 weeks compared to controls of same age but similar to controls and prenatal T-treated males at 30 weeks of age (P <0.05). Our findings suggest that prenatal T treatment advances the developmental trajectory of gonadal responsiveness to GnRH in male offspring.

Prazosin blocks the glutamatergic effects of N-methyl-D-aspartic acid on lordosis behavior and luteinizing hormone secretion in the estrogen-primed female rat

We have observed that intracerebroventricular (icv) injection of selective N-methyl-D-aspartic acid (NMDA)-type glutamatergic receptor antagonists inhibits lordosis in ovariectomized (OVX), estrogen-primed rats receiving progesterone or luteinizing hormone-releasing hormone (LHRH). When NMDA was injected into OVX estrogen-primed rats, it induced a significant increase in lordosis. The interaction between LHRH and glutamate was previously explored by us and another groups. The noradrenergic systems have a functional role in the regulation of LHRH release. The purpose of the present study was to explore the interaction between glutamatergic and noradrenergic transmission. The action of prazosin, an alpha1- and alpha2b-noradrenergic antagonist, was studied here by injecting it icv (1.75 and 3.5 µg/6 µL) prior to NMDA administration (1 µg/2 µL) in OVX estrogen-primed Sprague-Dawley rats (240-270 g). Rats manually restrained were injected over a period of 2 min, and tested 1.5 h later. The enhancing effect induced by NMDA on the lordosis/mount ratio at high doses (67.06 ± 3.28, N = 28) when compared to saline controls (6 and 2 µL, 16.59 ± 3.20, N = 27) was abolished by prazosin administration (17.04 ± 5.52, N = 17, and 9.33 ± 3.21, N = 20, P < 0.001 for both doses). Plasma LH levels decreased significantly only with the higher dose of prazosin (1.99 ± 0.24 ng/mL, N = 18, compared to saline-NMDA effect, 5.96 ± 2.01 ng/mL, N = 13, P < 0.05). Behavioral effects seem to be more sensitive to the alpha-blockade than hormonal effects. These findings strongly suggest that the facilitatory effects of NMDA on both lordosis and LH secretion in this model are mediated by alpha-noradrenergic transmission.

Evaluación del efecto agudo de la administración de GnRH sobre la secreción de leptina en mujeres sanas e hiperandrogénicas / Assessment of acute effect of GnRH administration on leptin secretion in normal and hyperandrogenic women

Background: Several studies suggest that leptin modulates the reproductive axis function. Leptin may stimulate release of GnRH from hypothalamus and of gonadotrophins from the pituitary. A synchronicity of LH and leptin pulses has been described in healthy women and in patients with polycystic ovarian syndrome (PCOS), suggesting a relationship between the episodic secretion of LH and leptin. In vitro experimental studies have demonstrated that leptin administration promotes GnRH-LH release. However it is not established whether GnRH promotes the episodic secretion of leptin. Aim: To assess the response of LH and leptin to the administration of a GnRH bolus in hyperandrogenic and healthy women. Patients and methods: Eleven hyperandrogenic and eleven healthy women of similar age and body mass index (BMI) were studied. Under basal conditions three blood samples were collected every 30 min before and after the administration of a GnRH bolus (100 µg). LH and leptin concentrations were measured in all samples. Testosterone, SHBG and estradiol were determined in the first sample. For data analysis, the increment of LH and leptin between 0-30 and 0-60 min. was calculated. The LH and leptin areas under the curve (AUC) before and after GnRH administration were also calculated in both groups. Results: After GnRH administration. an increment in LH concentrations was observed in both groups; however, leptin concentrations were not modified. In both groups LH area under the curve increased after GnRH administration; however, the leptin area was not modified. Conclusions: These results suggest that circulating leptin concentration is not modulated by GnRH-LH

¿Modulan los andrógenos la secreción de hormona luteinizante en mujeres? / Do androgens modulate luteinizing hormone secretion in women?

In hiperandrogenic states an abnormal pattern of LH secretion in women is observed, which is presumed to result from a direct action of androgen or its conversion to estrogen. Two strategies are available to study the effect of testosterona on LH secretion.One involves the use of non-steroidal compounds that block the negative feedback actions of endogenous androgens by binding to androgen receptors; the other consists only in the administration of androgens. Following these two strategies, we first studies the pulsatile gonadotrophin secretion in hyperandrogenic women, following flutamide administration, a specific androgen receptor blocker. Flutamide treatment was followed by a decrease in LH pulse amplitude and mean LH concentrations, demonstrating that androgen receptor blockade reduces LH secretion in hyperandrogenic women. To establish the level at which the androgen effect is exerted, we further studied the acute effect of testosterone (hyperandrogenic levels) and the blockade of its receptor on LH secretion in patients with severe hypothalamic deficiency treated with pulsatile GnRH (GnRHp). LH pulse profiles were assessed under GnRHp treatment alone, during testosterone and during testosterone and flutamide administration. Testosterone increased LH secretion and LH pulse amplitud. Flutamide significantly reverted the LH increase induced by testosterone.These results strongly suggest that testosterone in the hyperandrogenic female range, may facilitate LH secretion by the pituitary, effect that is reserved by the blockade of the androgen receptor

Effects cimetidine ranitidine and tiotidine on plasma testosterone and luteinizing hormone level in rats

The investigation was carried out to study the comparative effects of cimetidine, ranitidine and tiotidine on the plasma levels of testosterone and luteinizing hormone under local environmental conditions. The three H2- blocking drugs were injected to the adult male albino rats twice daily at the recommended therapeutic dose levels for six weeks. The data obtained showed that only tiotidine caused a significant [P< 0.05] increase in the level of testosterone. However, all the three drugs caused a significant rise in the levels of luteinizing hormone and maximum with ranitidine

Retardo puberal e hipogonadismo hipogonadotrófico: diagnóstico diferencial con la prueba de estimulación de prolactina con clorpromazina / Puberal delayed and hypogonadotrophic hypogonadism: differential diagnosis by prolactine stimulation with chlorpromazine test

We studied the changes in plasma levels of prolactin after an intramuscular injection of 0,33 mg/kg chlorpromazine and changes in plasma levels of LH and FSH after the injection of 100 µg iv GnRH in 16 patients with constitutional delayed puberty, 10 patients with hypogonadotrophic hypogonadism and 6 healthy controls. Prolactin response was significantly lower in patients with hypogonadotrophic hypogonadism compared to subjects with constitutional delayed and healthy controls ( prolactin 7.05ñ1.7, 28.9ñ2.7 and 22.0ñ3.4 ng/ml respectively). LH response to GnRH was also lower in patients with hypogonadotrophic hypogonadism, compared to the other groups ( LH 4.3ñ2.5, 13.4ñ5.4 and 17.2ñ4.8 mUI/ml respectively) however, there was a great overlapping of values. No differences between groups were observed in responses of FSH, testosterone and estrogens to GnRH. It is concluded that prolactin response to chlorpromazine is useful in the differential diagnosis of constitutional delayed puberty

Pode uma dose única de análogo do GnRH no primeiro dia do ciclo menstrual prevenir o aumento de LH na fase pré-ovulatória? / Can a single dose of the GnRH analogue on the first day of the menstrual period prevent the increase of LH in the preovulatory phase?

Neste estudo foi avaliada a hipótese pela qual uma única dose de análogo do GnRH no primeiro dia do ciclo menstrual preveniria o aumento do hormônio luteinizante (LH) na fase pré-ovulatória de um ciclo estimulado com gonadotrofina menopausal humana (hMG). Um total de 27 pacientes foi dividido em dois grupos. O grupo I (n=9) recebeu uma única dose de 4,0 mg de acetato de leuprolide no primeiro dia do ciclo menstrual. A estimulaçao ovariana foi realizada com hMG na dose de 150 UI no terceiro, quinto, setimo e nono dia do ciclo menstrual. Iniciou-se a monitorizaçao ultra-sonográfica do desenvolvimento folicular no décimo dia do ciclo. O grupo II (n= 18) foi submetido ao mesmo protocolo que o grupo I, com exceçao do análogo do GnRH que nao foi administrado. As doses de gonadotrofinas foram aumentadas em ambos os grupos até a observaçao de pelo menos um folículo > l7mm, quando uma amostra de sangue foi coletada para dosagem de LH, e a gonadotrofina coriônica humana foi administrada na dose de 10.000 UI. Os níveis plasmáticos de LH foram significativamente menores (p

Intracerebroventricular administration of canatoxin to rats increases the circulating levels of luteinizing hormone

Recent evidence has implicated the central nervous system as a target organ for canatoxin, a toxic protein present in Canavalia ensiformis seeds. This toxin activates the lipoxygenase pathway of arachidonic acid metabolism and can thus induce the release of substances mediated by lipoxygenase products. In the present study, the circulating levels of luteinizing hormone (LH) were measured by RIA in male Wistar rats (200-240 g) after the administration of canatoxin into the lateral cerebral ventricle. Canatoxin (0.5-2 micrograms in 2 microliters daily for 3 days) caused a dose- and time-dependent increase in the plasma levels of LH. The total dose of canatoxin used is subconvulsive. At 2, 4 and 24 h after 2 micrograms of canatoxin LH levels were increased by 10 per cent , 43 per cent and 61 per cent , respectively, compared to vehicle-injected animals (0.18 +/- 0.03 ng/ml). This response to 2 micrograms of canatoxin was not attenuated by pretreatment with two different lipoxygenase inhibitors, nordihydroguaiaretic acid (NDGA, 125 mg/kg) or esculetin (ECLT, 125 mg/kg), ip, 1 h before each canatoxin (CNTX) injection; per cent increase in LH with CNTX alone: 61 per cent ; CNTX+NDGA: 54 per cent ; CNTX+ECLT:76 per cent ; N = 5/group. These data show that intracerebral injection of CNTX in rats increases circulating levels of LH via a mechanism that is independent of the lipoxygenase pathway

Serum LH levels in the differential diagnosis of hirsute anovulatory women

Polycystic ovarian syndrome (PCO) occurs frequently in hirsute patients. A dissociated explosive response of LH to LHRH administration has been associated with the diagnosis of PCO. Twenty-four of 58 women seen because of hirsutism were found to have ovarian dysfunction based on clinical signs such as anovulation and irregular menstrual cycles. Plasma androgen levels were elevated in the patient group. The LHRH test (200 micrograms, iv) was applied to the 24 patients and compared with 13 normal ovulatory controls. Serum FSH levels before and after the LHRH test were normal in all patients. Two patterns of LH response to LHRH stimulation were observed: an explosive response in 17 patients (delta LH: 39.4 +/- 21.8 IU/l, control group: 7.35 +/- 4.4 IU/l, P < 0.01) and a normal response in 7 patients (delta LH: 7.53 +/- 2.41 IU/l). There was a significant correlation (r = 0.63, P < 0.05) between basal LH levels and LH response to LHRH. Sensitivity and specificity calculated for basal LH levels higher than 6.0 IU/l, considering the LHRH test as reference, were 58 per cent and 85 per cent , respectively. The positive predictive value measuring the possibility of LH higher than 6.0 IU/l to be from a patient with PCO (explosive response to LHRH) was 92 per cent . These data suggest that, in hirsute anovulatory patients, basal LH levels may be a good predictor in the diagnosis of polycystic ovarian syndrome

Análisis multifactorial de los niveles séricos de LH, FSH, y estradiol en relación a las tasas de captura ovular, fertilización y segmentación en pacientes de reproducción asistida (GIFT-FIVTE) / Multifactorial analysis of seric levels of LH, FSH and estradiol related to the ovular capture rates, fertilization and segmentation in patients of assisted reproduction (GIFT-FIVTE)

El presente estudio muestra que hay en la actualidad cierta tendencia a asignar mayor valor a la observación del crecimiento folicular por ultrasonido que a los niveles hormonales "per se". Sin embargo, la apreciación del crecimiento es sólo parte del fenómeno de desarrollo y madurez ovárica, por lo cual la vigilancia con monitor hormonal de la respuesta ovárica sigue teniendo un papel preponderante en las Clínicas de Reproducción Asistida. Los niveles basales principalmente de FSH y en menor grado los de LH, correlacionan inversamente con la cantidad de ovocitos recuperados. Los valores de estradiol deben interpretarse con un punto de referencia fijo, como el día de la administración de HCG y se aprecia una relación directa entre niveles de estradiol y ovocitos capturados; sin embargo, es de mayor utilidad valorar el comportamiento de la curva de estradiol, con el conocimiento de que el pronóstico para buenas tasas de captura mejora al presentarse valores ascendentes y por arriba de los 700 pg en el día de la administración de HCG.

Efeito do citrato de clomifene sobre a liberaçäo hipofisária de LH e FSH induzida pelo GnRH / Effect of clomiphene citrate on pituitary liberation of LH and FSH induced by GnRH

Com o objetivo de avaliar o mecanismo de açäo do citrato de clomifene (CO), dez mulheres hipogonádicas foram submetida à infusäo endovenosa contínua de GnRH nas seguintes condiçöes: sem qualquer medicaçäo (Teste I), após uso de CC (Teste II), após uso de etinil-estradiol (EE) (Teste III) e após uso de EE e CC (Teste IV). Os resultados mostraram que em condiçöes de hipoestrogenismo o CC näo modifica a resposta hipofisária de LH e FSH ao GnRH, mostrando uma leve açäo estrogênica. Entretanto, o uso de CC após estrogenioterapia promoveu diferentes respostas para o LH e FSH quando comparadas ao uso de EE isoladamente. Para o LH houve uma significante inibiçäo na sua liberaçäo, com menor sensibilidade, reserva e capacidade hipofisária. Para o FSH observou-se o oposto, com um incremento na sua liberaçäo, com maior sensibilidade e reserva hipofisária