Interactions of ovarian steroids with pituitary adenylate cyclase-activating polypeptide and GnRH in anterior pituitary cells.
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Pituitary adenylate cyclase-activating polypeptide (PACAP) releases LH and FSH from anterior pituitary cells. Although this effect is relatively weak, it has a strong sensitizing action on GnRH-induced gonadotropin secretion. Here we investigated the possibility that ovarian steroids, which are well-known modulators of LH secretion, interact with PACAP and GnRH in pituitary gonadotrophs. Rat pituitary cells were treated for 48 h with vehicle, 1 nmol/l estradiol, 1 nmol/l estradiol + 100 nmol/l progesterone or 48 h with 1 nmol/l estradiol and 4 h with 100 nmol/l progesterone. The cells were stimulated for 3 h with 1 nmol/l GnRH or 100 nmol/l PACAP. Estradiol treatment alone enhanced basal as well as GnRH- or PACAP-stimulated LH secretion. LH release was facilitated by additional short-term progesterone treatment. Long-term treatment with estradiol and progesterone led to reduced LH responses to GnRH and PACAP. Neither treatment paradigms affected cAMP production. However, estradiol treatment led to enhanced cAMP accumulation in quiescent or GnRH-stimulated cells. PACAP-induced increases of cAMP production were inhibited by estradiol treatment. After 7-h preincubation with 10 nmol/l PACAP, cells responded with enhanced LH secretion to GnRH stimulation. When steroid pretreatment was performed the responsiveness of gonadotrophs to low concentrations of GnRH was still increased. In contrast, at high concentrations of GnRH the sensitizing action of PACAP on agonist-induced LH secretion was lost in steroid-treated cells. There were no significant differences between the steroid treatment paradigms. It is concluded that estradiol but not progesterone acts as a modulator of adenylyl cyclase in gonadotrophs. The stimulatory effect of estradiol is thought to be involved in its sensitizing action on agonist-induced LH secretion. The inhibitory effect of estradiol on PACAP-stimulated adenylyl cyclase activities seems to be responsible for the loss of its action to sensitize LH secretory responses to GnRH. (+info)
The effect of chronic treatment with GH on gonadal function in men with isolated GH deficiency.
(34/6154)
Eleven adult males, previously submitted to neurosurgery because of a pituitary lesion (three with craniopharyngioma, three with clinically non-functioning adenoma and five with macroprolactinoma) were treated with recombinant GH for 12 months after the diagnosis of GH deficiency was made. Circulating FSH, LH, prolactin, testosterone, 17 beta-estradiol (E2), dehyroepiandrosterone (DHEA-S), androstenedione. 17-OH-progesterone (17OHP), IFG-I, and steroid hormone-binding protein (SHBG) levels were assayed before and after CG test at study entry and 6 and 12 months after GH treatment. A significant increase in plasma IGF-I levels was obtained after 6 and 12 months of GH treatment. In addition, CG-stimulated, but not baseline, testosterone levels showed a significant increase after 6 and 12 months of GH treatment when compared with study entry (9.6 +/- 0.5 and 9.9 +/- 0.5 vs 7.9 +/- 0.5 ng/ml; P < 0.05). Baseline, but not CG-stimulated, serum 17OHP levels were significantly increased only after 12 months of GH treatment (1.7 +/- 0.1 vs 1.4 +/- 0.1 ng/ml; P < 0.05). No significant difference was found as far as both basal and CG-stimulated E2, androstenedione, DHEA-S and SHBG were concerned. With regards to the semen analysis, only seminal plasma volume was significantly increased after 12 months of GH treatment (2.9 +/- 0.3 vs 1.7 +/- 0.3 ml; P < 0.05). No significant change in sperm count, motility and abnormal forms was observed. These data show that GH treatment displays a clear-cut effect upon Leydig cell function and increases the production of seminal plasma volume in fertile adult males with isolated GH deficiency. (+info)
Diagnostic difficulty in polycystic ovary syndrome due to an LH-beta-subunit variant.
(35/6154)
We initially failed to confirm a case of polycystic ovary syndrome (PCOS) because underestimation of LH concentrations due to a variant form of this hormone resulted in a misleadingly low LH/FSH ratio. A 26-year-old woman presented to our hospital with infertility. Given the presence of bilateral polycystic ovaries, oligomenorrhea and hirsutism. PCOS was suspected, but a normal LH/FSH ratio as measured by RIA led to diagnostic problems. When we remeasured LH and FSH using a chemical luminescence enzyme immunoassay (CLEIA), the ratio of the LH concentration measured by RIA to that measured by CLEIA was 0.29, and the ratio of LH to FSH measured by CLEIA was 3.3 compared with 0.81 measured by RIA. We then diagnosed PCOS. The point mutations Trp8 to Arg8 and Ile15 to Thr15 in the LH subunit were detected in the corresponding gene. The patient's LH status represented variant and wild-type LH equally. She was therefore diagnosed as heterozygous for the mutant LH-beta. Histologic assessment of ovarian tissue after laparoscopic biopsy was compatible with a polycystic ovary. (+info)
Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome.
(36/6154)
BACKGROUND: Women with the polycystic ovary syndrome have insulin resistance and hyperinsulinemia, possibly because of a deficiency of a D-chiro-inositol-containing phosphoglycan that mediates the action of insulin. We hypothesized that the administration of D-chiro-inositol would replenish stores of the mediator and improve insulin sensitivity. METHODS: We measured steroids in serum and performed oral glucose-tolerance tests before and after the oral administration of 1200 mg of D-chiro-inositol or placebo once daily for six to eight weeks in 44 obese women with the polycystic ovary syndrome. The serum progesterone concentration was measured weekly to monitor for ovulation. RESULTS: In the 22 women given D-chiro-inositol, the mean (+/-SD) area under the plasma insulin curve after the oral administration of glucose decreased from 13,417+/-11,572 to 5158+/-6714 microU per milliliter per minute (81+/-69 to 31+/-40 nmol per liter per minute) (P=0.007; P=0.07 for the comparison of this change with the change in the placebo group); glucose tolerance did not change significantly. The serum free testosterone concentration in these 22 women decreased from 1.1+/-0.8 to 0.5+/-0.5 ng per deciliter (38+/-7 to 17+/-3 pmol per liter) (P=0.006 for the comparison with the change in the placebo group). The women's diastolic and systolic blood pressure decreased by 4 mm Hg (P<0.001 and P=0.05, respectively, for the comparisons with the changes in the placebo group), and their plasma triglyceride concentrations decreased from 184+/-88 to 110+/-61 mg per deciliter (2.1+/-0.2 to 1.2+/-0.1 mmol per liter) (P=0.002 for the comparison with the change in the placebo group). None of these variables changed appreciably in the placebo group. Nineteen of the 22 women who received D-chiro-inositol ovulated, as compared with 6 of the 22 women in the placebo group (P<0.001). CONCLUSIONS: D-Chiro-inositol increases the action of insulin in patients with the polycystic ovary syndrome, thereby improving ovulatory function and decreasing serum androgen concentrations, blood pressure, and plasma triglyceride concentrations. (+info)
Effects of acute exposure to PCBs 126 and 153 on anterior pituitary and thyroid hormones and FSH isoforms in adult Sprague Dawley male rats.
(37/6154)
3,3'4,4',5-Pentachlorobiphenyl (PCB 126) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) were administered to adult male rats in order to identify sensitive indicators of endocrine disruption. We tested the hypothesis that PCB exposure modifies follicle-stimulating hormone (FSH) pituitary isoforms, as well as the pituitary and serum concentrations of FSH, luteinizing hormone (LH), growth hormone, prolactin, and thyroid-stimulating hormone (TSH). Effects on serum levels of thyroxine (T4) and testosterone (T), and prostate androgen receptor content, were also tested. In one experiment, 5 groups of 8 rats each received two i.p. injections, one day apart, of either corn oil or 6.25, 25, 100 or 400 micrograms/kg/day of PCB 126. Decreases (p < 0.05) in the serum concentrations of T4 and LH started at doses of 25 and 100 micrograms/kg/day, respectively. Serum FSH concentrations were reduced (p = 0.07) in the highest dose group. In contrast, pituitary content of FSH and LH increased with PCB-126 doses (p = 0.004, p = 0.002, respectively). Despite changes in reproductive hormones, PCB-126 had no effect on the androgen receptor content of the prostate. The effect of PCB-126 was tested in the hemicastrated rat, and suggested adverse effects on testosterone secretion. To test the effects of PCB exposure on FSH pituitary isoforms, 4 groups of 10 male rats received two i.p. injections, one day apart, of either corn oil, PCB 153 (25 mg/kg/day), estradiol-17 beta (E2; 20 micrograms/kg/day), or PCB 126 (0.1 mg/kg/day). Serum T4 levels were higher (p < 0.01) in the E2 and PCB 153 groups, and slightly reduced in the PCB 126-treated groups, compared to controls. Simultaneous purification of pituitary FSH and TSH isoforms was performed by HPLC, using two chromatofocusing columns in series. In contrast to TSH isoforms, the distribution of FSH isoforms over the chromatography run differed slightly between treatment groups; the amounts of FSH isoform eluted during the pH gradient were lower (p < 0.05) in E2 and PCB 153-treated rats than in control or PCB 126-treated rats. The similarity between the effects of E2 and PCB 153 on T4 and FSH isoforms supports the contention that PCB 153 possesses estrogenic properties. Serum LH and T4 concentrations were the most sensitive and practical endocrine indicators of PCBs 126 and 153 exposure in male rats. (+info)
Elevated serum progesterone on the day of HCG administration in IVF is associated with a higher pregnancy rate in polycystic ovary syndrome.
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Our study compared 84 patients with polycystic ovary syndrome (PCOS) with 84 control patients who had normal ovaries and who were matched for the main determinants of success in in-vitro fertilization (IVF) and embryo transfer. Serum concentrations of oestradiol and progesterone on the day of human chorionic gonadotrophin (HCG) injection were significantly higher in PCOS than in normal patients (oestradiol 2016 +/- 1.8 pg/ml versus 1456 +/- 40.9 pg/ml, P < 0.01; progesterone 1.6 +/- 0.1 ng/ml versus 1.2 +/- 0.1 ng/ml, P = 0.03). Furthermore despite oocytes from PCOS patients having a reduced fertilization rate compared with normal patients (61.8 +/- 4.1% versus 73.5 +/- 4.3%, P = 0.03), the differences in pregnancy rate (22.6 versus 19%) and miscarriage (31.5 versus 18.7%) were not statistically significant. In PCOS patients, a critical breakpoint was identified at serum progesterone concentrations of 1.2 ng/ml on the day of HCG injection. The PCOS patients with progesterone > or = 1.2 ng/ml showed a higher pregnancy and miscarriage rate than PCOS patients with progesterone < 1.2 ng/ml (26.6 versus 17.9%, P < 0.01; and 41.7% versus 14.3%, P < 0.01 respectively). These findings suggest that premature progesterone production does not have an adverse effect on pregnancy rate in PCOS, but on the contrary, may be a predictor for success in IVF/embryo transfer. (+info)
Changes in luteinizing hormone and insulin secretion in polycystic ovarian syndrome.
(39/6154)
Uncertainties regarding the pathogenetic changes underlying the polycystic ovarian syndrome (PCOS) have been reported. The aim of this study was to investigate the endocrine and metabolic features of PCOS patients in relation to luteinizing hormone (LH) secretion. Androgen assays, oral glucose tolerance tests, hyperinsulinaemic euglycaemic clamps and gonadotrophin releasing hormone (GnRH) tests were performed in 100 patients. Sixty-six patients scheduled as hyperinsulinaemic and 34 as normoinsulinaemic showed similar concentrations of LH, follicle stimulating hormone (FSH), LH/FSH ratio, and LH response to GnRH testing. Hyperinsulinaemic subjects showed higher body mass index (BMI), insulin resistance, testosterone and free androgen index levels compared with those of normoinsulinaemic subjects; when clustered in relation to their LH basal concentrations, the two groups obtained differed only in androstenedione concentrations. Considering both insulin and LH plasma concentrations, four groups were obtained. Hyperinsulinaemia and hyper-LH secretion were not related in 54% and coexisted in the same subjects in 26% of cases. Hyperinsulinaemia as well as hyper-LH secretion affected the expression of the syndrome; the insulinaemia was directly correlated with testosterone concentrations and all metabolic parameters that affected the free androgen index. The LH concentrations were related to androgen production and were independent of BMI and insulin concentrations. It is concluded that the degree of hormonal alteration is the final sum of such pathogenetic factors. (+info)
Ovarian stromal echogenicity in women with normal and polycystic ovaries.
(40/6154)
Since the widespread use of transvaginal ultrasound to diagnose polycystic ovary syndrome (PCOS), a cardinal feature has been shown to be the presence of a bright, highly echogenic stroma. This is usually assessed subjectively. The objective of this study was to determine whether ovarian stromal echogenicity when measured objectively actually differed between women with polycystic ovaries and those with normal ovaries. A total of 67 women underwent a detailed ultrasound assessment before considering assisted conception treatment. Ovarian morphology was assessed and total ovarian volume, stromal volume, peak stromal blood flow velocity and mean stromal echogenicity were measured. The stromal index (ratio of mean stromal echogenicity to mean echogenicity of the entire ovary) and total stromal echogenicity were also calculated. Ovarian volume, stromal volume, and stromal peak blood flow velocity were all significantly higher in ovaries from women with PCOS. There was no difference in the mean stromal echogenicity, although the stromal index was significantly greater in women with polycystic ovaries. The apparent subjective increase in stromal echogenicity in women with polycystic ovaries, as exemplified by the greater stromal index, is due to a combination of the increased volume of ovarian stroma and the significantly lower mean echogenicity of the entire ovary in these women. (+info)