Metabolic and endocrine consequences of acute suppression of FFAs by acipimox in polycystic ovary syndrome.

To evaluate the effects of acute lowering of FFAs on glucose-induced insulin secretion and GH response to GHRH in polycystic ovary syndrome (PCOS), 27 PCOS subjects (11 lean and 16 obese) and 17 body mass index-matched controls (8 lean and 9 obese) were investigated. Patients underwent an oral glucose tolerance test and a GHRH test before and after administration of the antilipolytic drug acipimox (250 mg orally 3 h and 1 h before the starting of the tests). Blood samples were collected for 2 h after GHRH bolus and for 4 h after the oral glucose tolerance test. Serum concentrations of GH, insulin, glucose, and c-peptide were assayed in each sample, and the results were expressed as area under the curve (AUC). No significant differences were found as to glucose, insulin, and c-peptide AUC before and after acute FFA plasma reduction in any of the investigated groups. Basally, lower GH-AUC was found in lean PCOS compared with body mass index-matched controls and in obese vs. lean controls; no significant differences were found as to the same variable between the two obese groups. The acipimox induced FFA suppression elicited in the four groups a sustained increase in the GH response to its trophic hormone; indeed, the GH-AUC nearly doubled with respect to basal evaluation in all the studied groups. However, the antilipolytic drug was not able to abolish the differences found between lean groups in basal conditions. In conclusion, the presented data confirm that FFAs have a main role in regulating GH secretion at the pituitary level; however, it does not seem that they could explain the GH as well as insulin dysfunction of PCOS.

Allopregnanolone and dehydroepiandrosterone response to corticotropin-releasing factor in patients suffering from Alzheimer's disease and vascular dementia.

OBJECTIVE: Neurosteroids have been suggested to be involved in the regulation of cognitive performances. A major neurosteroid gamma-aminobutyric acid (GABA) agonist is allopregnanolone: the main source of circulating allopregnanolone is the adrenal cortex. Studies indicated that a disturbance of the central regulation of the hypothalamic-pituitary-adrenocortical axis occurs in both senile (Alzheimer's disease: AD) and vascular dementia (VD). DESIGN: The aim of the present study was to evaluate the levels of circulating allopregnanolone, dehydroepiandrosterone (DHEA) and cortisol and their response to corticotropin-releasing factor (CRF) test in AD and VD. METHODS: Three groups of 12 subjects were included in the study: AD, VD and age-matched control subjects. CRF test was performed in all subjects and allopregnanolone, DHEA and cortisol levels were measured every 15min for 2h. RESULTS: Mean +/- s.e.m. allopregnanolone and DHEA basal levels were significantly lower in AD and VD than in controls, while cortisol levels were significantly higher than in controls (P<0.01). Allopregnanolone and DHEA levels increase in response to CRF test in all subjects but the area under curve (AUC) in patients was significantly lower than in controls (P<0.01). Cortisol secretion appeared to be very sensitive in response to CRF stimulation: in fact, cortisol response to CRF test in AD and VD subjects was higher (both as AUC and as % max increase) than in controls (P<0.01). CONCLUSIONS: The present study firstly showed that allopregnanolone levels are reduced both in AD and in VD and that dementia has a preserved stimulated response of allopregnanolone to CRF. Overall, however, the total response of allopregnanolone to CRF remains reduced in respect to controls. Further studies are necessary for a better understanding of the role of neurosteroids in the regulation of cognitive function.

Postmenarchal Down's syndrome: a theoretical model of growth hormone action on ovarian function.

Much evidence indicates that blunted ovarian sensitivity to follicle-stimulating hormone (FSH) and lower growth hormone (GH) plasma concentrations, as often occur in women with Down's syndrome (DS), may contribute to the gonadal disfunction frequently present in such subjects. In this review, we analyze the more recent advances in this field, and then discuss from a clinical point of view the potential role of GH on ovarian function, since DS patients may also constitute a theoretical model for investigating this particular aspect of reproductive physiology.

Neuroendocrine features of pubertal development in females with mental retardation.

In order to evaluate the hypothalamic-pituitary effects of mental retardation during pubertal development, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) responses to gonadotropin-releasing hormone (GnRH) administration were evaluated at various pubertal stages in a female population with mental retardation (MR) compared to a healthy control group of adolescents. Fifty-six girls aged 8-16 years with MR and 146 normal females of the same age participated in the study. The analyzed subjects were divided into different pubertal stages, ranging from P2 to P5, in line with their degree of sexual maturation. Each patient underwent a GnRH test (100 micrograms); blood samples were collected basally and 15, 30, 60, 90 minutes after the GnRH injection. FSH and LH were assayed in each sample; the gonadotropin response to GnRH administration was evaluated as incremental area. No differences were found at any pubertal stage between the two studied groups with regard to the age, body mass index, or age at menarche. Patients with mental retardation during stages P2 and P3 showed lower FSH secretion in response to GnRH bolus compared with control subjects (P2, p < 0.05; P3, p < 0.01). In conclusion, our data show that MR is related to an impaired response of the FSH-secreting pituitary cells to their appropriate stimulus; this feature is present only in the initial pubertal stages, whereas it disappears during sexual development.

Bilateral non-communicating paraurethral meatus in Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a complex multisystemic congenital disorder due to an interstitial deletion of chromosome 15q11-13 or to maternal uniparental disomy. Molecular genetic testing is complex, and often requires DNA from both parents, which is not always available. An accurate medical history and presenting clinical signs are frequently the only tools for the clinical diagnosis of this syndrome, therefore it is important to have complete and accurate criteria. The presence of a bilateral non-communicating paraurethral meatus in a 9-year-old female patient affected by PWS, previously unreported in the literature, should induce clinicians to look for this sign when examining such patients.

Basal body temperature curves and endocrine pattern of menstrual cycles in Down syndrome.

We examined the basal body temperature curves and the endocrine pattern of 20 cycles from women with Down syndrome with regular menstrual cycles. Data were compared with those obtained from an age-matched population of healthy women with regular menses. Growth hormone deficiency was excluded for women with Down syndrome by pharmacological tests. Women with Down syndrome showed a significantly higher incidence of anovulation and luteal defects than controls (p < 0.001). Overall, and in ovulatory cycles, estradiol and progesterone plasma levels were greater in controls than in women with Down syndrome. No difference was observed for gonadotropin and androgen circulating levels between the two groups. It is concluded that in women with Down syndrome with regular menses, ovulatory events were less frequent and often characterized by luteal defects. This could be ascribed to an impairment of both follicular and luteal functions. However, reproduction is possible in such patients.

Ovarian sensitivity to follicle stimulating hormone is blunted in normo-ovulatory women with Down's syndrome.

Ovarian sensitivity to follicle stimulating hormone (FSH) during the early follicular phase of the human menstrual cycle was studied in six post-menarchal patients with Down's syndrome and 12 normo-ovulatory women. Pure FSH (75 IU) was given i.v. to six controls and six Down's syndrome patients, while saline was administered to the remaining six controls. Plasma concentrations of luteinizing hormone (LH), FSH, oestradiol, testosterone and growth hormone (GH) in samples collected for a period of 26 h after the injection were assayed. In control patients FSH injection increased oestradiol stimulated area under the curve (AUC). This value was significantly higher than that found in Down's syndrome patients (P < 0.02), who exhibited an oestradiol-stimulated AUC equivalent to saline-treated controls. In Down's syndrome, GH plasma concentrations were significantly lower than in the control group (P < 0.05). These results indicate that the ovarian sensitivity to FSH in patients with Down's syndrome is blunted. Lower GH plasma concentrations found in this group may in part account for this biological feature.

Serum leptin concentrations in obese women with Down syndrome and Prader-Willi syndrome.

We have evaluated serum leptin concentrations in two forms of genetic obesity. The subjects examined were eight women with Down syndrome and eight women with Prader-Willi syndrome. All patients were in the reproductive age range and were obese (body mass index > or = 27 kg/m2). Plasma leptin values, analyzed as a function of body mass index showed a statistically significant correlation in both Prader-Willi (r = 0.985; p < 0.001) and Down syndrome patients (r = 0.943; p < 0.001). Obese Down syndrome women exhibited significantly lower leptin values (10.8 +/- 1.1) as compared to patients with Prader-Willi syndrome (31 +/- 2.6; p < 0.01). The linear correlation between leptin and insulin in the two groups of patients was not statistically significant. The data suggested that obesity in Prader-Willi subjects could be caused by failure of leptin to reach its target in the brain, as a consequence of defects in the receptor or in postreceptor processing, whereas data on obese patients with Down syndrome could be due to a different pathogenetic origin.

Growth hormone administration normalizes the ovarian responsiveness to follicle-stimulating-hormone in the early stages of the follicular maturation in women with Down syndrome.

To investigate the sensitivity of ovary to follicle-stimulating hormone (FSH) during the early follicular phase of the human menstrual cycle in patients with Down Syndrome (DS) six postmenarchal patients with Down Syndrome and twelve normoovulatory women were studied. Randomly, DS patients were submitted in two consecutive cycles to a treatment with GH (0.1 IU/Kg i.m.) or saline for 3 days. Pure FSH (75 IU) was given i.v. at day 3 and plasma levels of LH, FSH, E2, Testosterone, DHEAS, Androstenedione, GH and IGF-I were assayed in samples collected for a period of 26 h after the injection. Data were compared with those obtained from controls receiving pure FSH or saline. In control patients FSH injection increased E2 stimulated area under curve (AUC). This value was significantly greater than that found in DS patients, who exhibited an E2-stimulated AUC superimposable to saline treated controls. In DS GH plasma concentrations were significantly lower than in control group (p < 0.05). The treatment with GH is able to normalize the ovarian response to FSH in DS patients at levels similar to those found in FSH treated controls. Moreover in GH treated cycles, both GH and IGF-I plasma concentrations were higher at time of FSH injection with respect to those found in the cycles where saline was given. These results indicate that the ovarian sensitivity to FSH in patients with DS is blunted. Lower GH plasma levels found in this group may in part account for this biological feature, since GH treatment is able to restore the ovarian response, probably via an increase of IGF-I plasma concentrations.

Leptin levels in menopause: effect of estrogen replacement therapy.

To evaluate the effect of menopause and estrogen replacement therapy on leptin levels, 17 white postmenopausal women were recruited for the study. After an overnight fasting, blood samples were collected for LH, FSH, estradiol, testosterone, androstenedione, DHEA sulfate, insulin and leptin assays. Body mass index (BMI) and the waist-to-hip ratio were also evaluated. Patients were reanalyzed after a 12-week administration of transdermal estrogen patches delivering 50 microg 17beta-estradiol. The results were compared to those obtained from a group of 11 female volunteers in reproductive age, in whom basal blood was sampled during the early follicular phase of their cycle. Patients were divided into lean and obese according to their BMI. Obese postmenopausal women showed lower leptin levels when compared to premenopausal counterparts (25.1 +/- 5.9 vs. 37 +/- 11.3; p < 0.05), whereas no significant differences were found between the lean groups (14.5 +/- 3.8 vs. 14.4 +/- 4.9). Estrogen administration did not significantly change serum leptin concentrations in hypoestrogenized women (obese: 25.1 +/- 5.9 vs. 28. 6 +/- 9.2; lean: 14.4 +/- 4.9 vs. 17.6 +/- 7.2). A positive linear correlation was found between leptin plasma levels and BMI only in obese patients (r = 0.58; p < 0.01) both before and after estrogen treatment. Menopause is characterized by a decreased expression of the obese gene, even if estrogens do not seem to represent a main causal factor.