Opioid control of gonadotrophin secretion in humans.

Hypothalamus-pituitary-axis (HPA) is constantly under the modulatory effect of many substances, such as neurotransmitters, neuromodulators and steroid hormones. Recently, the involvement of endogenous opioid peptides (EOP) in the control of the neuroendocrine mechanism modulating gonadotrophin secretion has been supported by several authors. It has been demonstrated that acute morphine administration decreases luteinizing hormone (LH) plasma levels and this is due to an inhibitory modulation on gonadotrophin releasing hormone discharge from the hypothalamic neurons. EOP are usually increased by stressful situations. In stress-induced amenorrhoea, the presence of low LH plasma levels and an abnormal LH pulsatile secretion has been related to an increased opioid activity, thus supporting the integrative role of opioids between hormonal and neuronal afferences of brain.

Growth hormone treatment affects plasma LH pulsatile release in women with secondary amenorrhoea.

OBJECTIVE: Since growth hormone (GH) is administered as a co-gonadotrophic factor in ovulation induction, this study aimed to assess the action of GH on the episodic pulsatile release of LH and FSH in amenorrhoeic patients. PATIENTS AND DESIGN: Nineteen patients affected by hypothalamic amenorrhoea were enrolled for this study: group A, 9 patients with normal gonadotrophins; group B, 10 patients with low gonadotrophins. Both groups were studied during GH infusion (0.015 IU/min for 4 hours) and after 7 days of GH administration (0.1 IU/kg/day). Patients underwent a 4-hour pulsatility study, with blood sampling every 10 minutes. A standard GnRH test (10 micrograms i.v. bolus) was performed immediately after the pulsatility evaluation. MEASUREMENTS: LH and FSH were assayed with an IFMA method; oestradiol and IGF-I were assayed by RIA and IRMA, respectively. PULSE DETECTION: Time series were analysed with Detect program. RESULTS: All patients showed similar LH and FSH pulsatile characteristics both under baseline conditions and during GH infusion. After 7 days of GH administration, episodic FSH release showed no change in either group. On the contrary, LH pulse frequency (mean +/- SE) significantly increased in group A (4.0 +/- 0.2 peaks/4h, P < 0.05), while pulse amplitude (baseline, 3.9 +/- 0.6 IU/l; after 7 days, 2.9 +/- 0.3 IU/l, P < 0.05), and integrated LH plasma concentrations (baseline, 7.6 +/- 1.1 IU/l; after 7 days, 5 +/- 0.8 IU/l, P < 0.05) were significantly decreased. No significant changes were observed for LH pulse frequency, amplitude or integrated LH plasma concentrations in hypogonadotrophinaemic patients (group B). Plasma oestradiol levels were significantly increased only in group A (baseline, 154.18 +/- 23.8 pmol/l; after 7 days, 380.3 +/- 110.1 pmol/l, P < 0.05), while IGF-I levels were significantly increased in both groups after 7 days of GH administration (P < 0.05). No significant differences were observed in the gonadotrophin responses to GnRH test before and after GH administration. CONCLUSIONS: The present study showed that the administration of GH in amenorrhoeic patients determines the significant changes in episodic LH release in those subjects with normal LH plasma levels and suggests that the action of GH may be dependent upon the ovarian-pituitary feedback action.

Modulatory role of estrogens and progestins on growth hormone episodic release in women with hypothalamic amenorrhea.

OBJECTIVE: To define the characteristics of spontaneous GH episodic secretion and the modulatory role of gonadal steroids in patients with hypothalamic amenorrhea associated with weight loss. DESIGN: Women were studied for 8 hours, sampling every 10 minutes, and plasma GH levels were measured by RIA. SUBJECTS: Fifteen patients with weight-loss-related amenorrhea were studied in baseline conditions. Five out of 15 patients underwent two cycles of hormonal replacement therapy with E2 patches (100 micrograms every 3 days for 24 days) and medroxyprogesterone acetate (MPA) (10 mg/d, from day 12 to day 24). On the second cycle of therapy, the pulsatility study was repeated twice: after only estrogen (day 11) and after E2 plus progestin (day 22). Four normally cycling women were studied as a reference group during midfollicular and midluteal phases. RESULTS: Amenorrheic patients showed mean plasma GH levels similar to healthy women during the follicular phase but significantly lower than those observed during the luteal phase. GH pulse frequency was higher in patients than in controls, whereas pulse amplitude was comparable with the follicular phase but lower during the luteal phase. During the hormonal replacement therapy, when only E2 was administered, GH pulse frequency decreased, whereas GH integrated plasma concentrations and GH pulse amplitude increased significantly. After MPA and E2 administration, GH pulse amplitude and GH plasma levels decreased, which was similar to pretreatment condition. CONCLUSIONS: The present study demonstrated that in amenorrhea associated with weight loss the frequency of GH episodic release is significantly higher than in normally cycling women. Moreover, a different modulatory role of estrogen (increased amplitude) and P (decreased amplitude) on the episodic release of GH in amenorrheic women undergoing a replacement treatment was shown by the present data.

The concomitant release of androstenedione with cortisol and luteinizing hormone pulsatile releases distinguishes adrenal from ovarian hyperandrogenism.

Androstenedione secretory characteristics and its possible temporal correlation with luteinizing hormone (LH) and/or cortisol, intended as the markers of, respectively, ovarian stimulation and adrenal secretion, were evaluated in 24 patients affected by clinical hyperandrogenism. A pulsatility test was carried out for 8 h, with sampling every 10 min, and LH, cortisol and androstenedione profiles were determined by radioimmunoassay. Time series were analyzed with the computer program DETECT and with a program for specific concordance estimation. A distinct episodic release of LH, cortisol and androstenedione was observed in all patients (6.9 +/- 0.8, 5.2 +/- 0.6 and 5.5 +/- 1 peaks/8 h, respectively). When specific concordance was tested between LH and androstenedione, and between cortisol and androstenedione, two distinct groups of patients could be identified. Group A (n = 13) showed a significant specific concordance (SC) index only for LH and androstenedione while group B (n = 11) showed a significant SC also for cortisol and androstenedione, thus demonstrating a consistent adrenal participation in the androstenedione secretion in these patients. In addition, specific differences were observed on androstenedione secretory profiles of group B which showed a significant (p < 0.05) decrease of androstenedione plasma concentrations emulating cortisol behavior. No such observation was noted in group A, whose androstenedione plasma levels did not show any reduction. In conclusion, our data support the use of circulating androstenedione, LH and cortisol plasma levels and copulsatile assessment to distinguish the presence of two populations of hyperandrogenic patients: one whose hyperandrostenedionemia is mainly due to ovarian secretion (group A) and one which showed a hyperactivation of the adrenal gland (group B).(ABSTRACT TRUNCATED AT 250 WORDS)