Spontaneous episodic release of adenohypophyseal hormones in hypothalamic amenorrhea.
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Amenorrhea↗
Biomedical subjects
A D Genazzani
Publications and source records attributed to A D Genazzani.
Secretion and putative role of activin and CRF in human parturition.
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Activins↗
The duration of prolactin secretory bursts from the pituitary is independent from both prolactin and gonadal steroid plasma levels in women and in men.
The intrinsic secretory characteristics of prolactin (PRL) have been investigated using newly developed algorhythms for instantaneous secretory rate (ISR) computation. PRL secretory rate, its intrinsic pulsatile characteristics and their possible dependance from gonadal steroids were investigated in five groups of subjects: a) 11 women during the follicular and luteal phase of the same menstrual cycle; b) 5 healthy postmenopausal women; c) 6 women affected by functional hyperprolactinemia; d) 5 normal men; e) 4 agonadal subjects before and during testosterone replacement therapy. All subjects underwent a 6 hours pulsatility study, from 08:00 to 14:00, sampling every 10 minutes. PRL plasma concentrations were determined using a RIA system and the presence of PRL secretory pulses was evaluated with program DETECT, both on plasma time series and after ISR computation. A distinct PRL episodic release was observed in all groups (follicular phase: 5.5 +/- 0.5, luteal phase: 6.5 +/- 0.6, postmenopause: 5 +/- 1, hyperprolactinemic women: 4.2 +/- 0.8, men: 4.8 +/- 0.4, agonadal before testosterone: 6 +/- 1, agonadal during testosterone administration: 5.3 +/- 0.3 peaks/6h), but mainly the computation of ISR allowed to demonstrate that the duration of the lactotropes secretory events was constant in all groups studied. PRL secretory bursts duration ranged between 23.1 +/- 1.8 and 25.4 +/- 2.5 minutes independently both on PRL or on sex steroid plasma levels. In conclusion, the present report shows that in different physiological conditions the intrinsic secretory bursts from lactotropes are constant in duration independently from the functional state, sex and the steroid hormone levels.
Adult↗
Life events impact in patients with secondary amenorrhoea.
To evaluate the relationship between stressful life events and the onset of secondary amenorrhoea Paykel's semi-structured interview for Recent Life Events was administered to patients affected by secondary amenorrhea and also to healthy volunteers. The number, quality, and objective negative impact of life events were compared among different hormonal subtypes of secondary amenorrhoea and healthy normally menstruating women, as a control group. The number of life events in amenorrhoeic patients (N = 131) was significantly greater than those observed in the control group (N = 64) (45.9 vs 32.8%). Moreover, where only hypothalamic hypogonadotrophic amenorrhoea was considered, the occurrence of life events was significantly higher (59.8%) than in hyperandrogenic (26.6%) or in normogonadotrophic (20.4%) patients. The most prevalent events among hypothalamic hypogonadotrophic amenorrhoeic patients were those classified as 'undesirable', 'uncontrolled' and with 'Objective Negative Impact'. The present study supports the hypothesis of a cause-effect relationship between stressful personal life events and the onset of secondary amenorrhoea of hypogonadotrophic subtype.
Adaptation, Psychological↗
Evidence suggesting an additional control mechanism regulating episodic secretion of luteinizing hormone and follicle stimulating hormone in pre-pubertal children and post-menopausal women.
The possible differential regulation of pulsatile follicle stimulating hormone (FSH) and luteinizing hormone (LH) secretion in pre-pubertal children and in post-menopausal women was investigated. Children were studied for 4 h and post-menopausal women for 6 h; blood samples were taken every 10 min. Post-menopausal women were studied before and 21 days after administration of a single i.m. dose of gonadotrophin-releasing hormone (GnRH) analogue. Eight post-menopausal women and 18 children (nine boys and nine girls) were enrolled. The children were divided into two groups: A, at Tanner stages 0-1 (four boys and three girls); B, at Tanner stage 2-3 (five boys and six girls). Plasma LH and FSH concentrations were determined using an immunofluorimetric assay. Time series were analysed and the specific concordance (SC) index was computed to determine the degree of concordance between episodes of LH and FSH secretion. While children of group A had LH concentrations below the minimal detectable dose of 0.1 IU/l, group B showed measurable LH plasma concentrations (1.4 +/- 0.3 IU/l, mean +/- SEM). Plasma FSH concentrations were detectable in both groups. Group A showed FSH plasma concentrations significantly lower than those of group B (0.75 +/- 0.2 and 1.95 +/- 0.4 IU/l respectively; P < 0.05), but FSH pulse frequency was higher in group A (P < 0.05). Children of group B showed significant concomitance of LH and FSH secretory events at time 0 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Episodic changes of serum procollagen type I carboxy-terminal propeptide levels in fertile and postmenopausal women.
The aim of the present study was to optimize the use of serum procollagen type I carboxy-terminal propeptide (PICP) as a possible marker of postmenopausal-376lted changes of bone metabolism. Postmenopausal (n = 20) and healthy fertile young (n = 4) women were studied after informed consent. The postmenopausal women were subdivided in 4 groups: (1) nontreated; (2) treated with estrogen-progestogen replacement therapy; (3) treated with calcitonin, or (4) with kidney or liver diseases. Blood samples were collected at 15-min time intervals for 4, 6 or 8 h. Serum concentration of PICP was measured by radioimmunoassay, in duplicate at two different dilutions. In postmenopausal women mean +/- SEM serum PICP levels were slightly but nonsignificantly higher than in fertile women. Serum PICP levels in estrogen-progestogen or calcitonin-treated women were significantly lower than in non-treated postmenopausal women. Episodic changes of circulating PICP level were observed in fertile and postmenopausal women. The pulses of serum PICP levels did not show significant differences among the groups of women studied. The present study showed that the measurement of serum PICP levels is a useful marker for investigating the changes of bone metabolism. In particular, low PICP levels in postmenopausal women under steroid hormone or calcitonin treatment in part reflect the changes of bone turnover. The pulses of serum PICP levels during a time interval suggest that collagen metabolism in women undergoes a rapid turnover.
Adult↗
Intrinsic secretory characteristics of luteinizing hormone and prolactin episodic release during pubertal development.
The intrinsic characteristics of LH and prolactin (PRL) episodic secretion were evaluated in a group of 18 children (8M and 10F). The children were divided into two groups according to the Tanner stage: Group A (Tanner < or = 1, N = 7, 3M and 4F, 6-10 years of age) and group B (Tanner 2-3, N = 11, 5M and 6F, 9-11 years of age). A pulsatility study of 4 h, sampling every 10 min, was carried out in all children. LH and PRL plasma levels were assayed by IFMA and RIA respectively. LH and PRL secretory episodes were then identified on plasma determinations using the program DETECT. Instantaneous secretory rates (ISR) were then computed for both LH and PRL using the specific algorithm within the DETECT program. Plasma LH levels were different between the two groups of children. Group A children showed undetectable LH plasma levels (below the minimal detectable dose of 0.1 mIU/ml), while group B demonstrated LH plasma levels in the normal range of values for age and sexual development (1.5 +/- 0.3 mIU/ml, mean +/- SEM). LH pulse frequency for group B was 3.2 +/- 0.4 peaks/4 h. No significant differences in mean plasma PRL levels, pulse frequency and pulse amplitude were observed between the two groups of children. Computation of ISR for LH (group B only) and PRL (both groups) identified the intrinsic episodic characteristics of the two hormones. No significant differences in LH and PRL pulse frequencies were observed when comparing the results estimated on ISR with those estimated on plasma concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Analysis of Variance↗
Pulsatile fluctuations of plasma-gonadotropin-releasing hormone and corticotropin-releasing factor levels in healthy pregnant women.
Several data emphasize the neuroendocrine aspects of human placenta. Classical hypophyseotropic neurohormones are produced and secreted by the human placenta. Indeed, in contrast with non pregnant subjects, gonadotropin-releasing hormone (GnRH) and corticotropin-releasing factor (CRF) are measurable in maternal plasma during pregnancy. The aim of the present study was to investigate the characteristics of the secretory pattern of maternal plasma GnRH and CRF levels. A total of 25 healthy pregnant women participated in the present cross-sectional study. Plasma levels of the two neurohormones were measured according to three different time-intervals: 1) every five minutes for eight hours (n = 4), 2) every ten minutes for four hours (n = 15), 3) every four hours for 24 hours (n = 7). Following an acidic extraction plasma GnRH and CRF levels were measured by specific radioimmunoassay. Using two different algorithms (Detect and Cluster) a pulsatile pattern for both plasma GnRH and CRF levels was observed. Specific pulse frequency, amplitude, and duration were found. In the groups of women studied with a longer sampling interval, pulse frequency of GnRH or CRF levels did not differ between first and third trimester of gestation. However, amplitude of CRF pulses were significantly higher at term than at early stages of pregnancy (p < 0.01), while GnRH pulse amplitude was highest in women at first trimester of gestation. Evaluating the degree of concordance in all subjects, GnRH pulses significantly correlated with CRF pulses at 30 min. lag (p < 0.01). No significant circadian changes were found for any circulating neurohormone measured.(ABSTRACT TRUNCATED AT 250 WORDS)
Algorithms↗
Episodic release of prolactin in women with weight loss-related amenorrhea.
Amenorrhea associated with weight loss is characterized by several neuroendocrine aberrations. The aim of the present study was to define the characteristics of episodic secretion of prolactin in women with weight loss-related amenorrhea. To evaluate whether hypoestrogenism was responsible for the changes in prolactin secretion in amenorrheic women, the pulsatile secretory pattern was also studied during hormone replacement therapy (HRT). Fifteen patients were studied by blood sampling every 10 min for 8 h. Four normally cycling women were studied as a reference group, during both the midfollicular and midluteal phases. Mean plasma prolactin levels and pulse amplitude were lower in amenorrheic patients than in controls. The prolactin pulse frequency was higher than that in controls during the follicular phase, but lower than controls during the luteal phase of the menstrual cycle. During HRT, mean plasma prolactin levels significantly increased, pulse frequency decreased and pulse amplitude significantly increased both during estradiol and estradiol plus medroxyprogesterone acetate administration. In conclusion, in amenorrhea associated with weight loss the chronobiological organization of prolactin secretion is deranged, both as a result of a neuroendocrine alteration and as a result of low plasma levels of gonadal steroids.
Amenorrhea↗
A comparative study of three ovulation induction protocols in polycystic ovarian disease patients in an in vitro fertilization/embryo transfer program.
PURPOSE: This study compares the results of three ovulation induction protocols in polycystic ovarian disease (PCOD) patients undergoing an in vitro fertilization-embryo transfer (IVF-ET) program. A total of 85 cycles was studied. The patients were treated with clomiphene citrate (CC) plus human menopausal gonadotropin (hMG) (CC/hMG group), with purified menofollitropin (pFSH) plus hMG (pFSH/hMG group), and with pFSH/hMG plus gonadotropin releasing hormone analogue (GnRH-a) (analogue group). In the analogue group the suppression of luteinizing hormone (LH) with GnRH-a decreased the number of follicles < 12 mm on the day of human chorionic gonadotropin (hCG) administration and the number and percentage of immature oocytes retrieved and increased the percentage of mature oocytes retrieved. RESULTS: However, fertilization rates of oocytes, cleaved embryo rates, pregnancy rates following replacement, and pregnancy outcomes were not different. CONCLUSION: Although the suppression of the hypothalamic-pituitary-ovarian axis with GnRH-a in PCOD patients improved follicular synchrony and oocyte maturity, none of the ovulation induction protocols was superior to the others with respect to pregnancy rates and pregnancy outcomes.
Adult↗
Contraception in older woman.
Oral contraception (OC) in the premenopause has been recently proposed as treatment for control and prevention of the putative symptoms typical of this period of life. Indeed, menstrual cycle disturbances and climacteric symptoms frequently occur at this age. The major aim of normal contraception is resultant maintenance of normal sexual activity. The effects of one OC containing 20 mcg ethinylestradiol and 150 mcg desogestrel (EE/DOG) were studied. Treatment did not significantly modify both lipid metabolism (triglycerides, total cholesterol, HDL, LDL, Apo A, Apo B) and clotting system (fibrinogen, PT, PTT, antithrombin III, fibrinopeptide A). No significant modifications of oral glucose tolerance test (OGGT) occurred after EE/DOG treatment. Also, bone density was not modified during estro-progestinic administration. From our experience, if there are no risk factors such as smoking, obesity or hypertension, the OCs could be used until menopause for absolute contraceptive efficacy, good tolerance and lack of side effects.
Adult↗
Corticotropin-releasing hormone modulates cytokines release in cultured human peripheral blood mononuclear cells.
Immune and neuroendocrine systems interact at various levels. In particular, either cytokines activate the hypothalamus-pituitary-adrenal axis (HPA) or corticotropin-releasing hormone (CRH) induces the release of beta-endorphin from peripheral human mononuclear cells. The aim of the present study was to investigate whether CRH may affect cytokine production and activity in human peripheral blood mononuclear cells (PBMC). Primary cultures of human PBMC and monocytes were used. They were incubated in presence of different doses of synthetic human CRH. Media were collected and interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) levels were measured by ELISA, while interferon-gamma (IFN-gamma) levels were measured by bioassay. In addition, phytohemoagglutinin-induced lymphocyte proliferation was evaluated by testing [3H]thymidine incorporation in the presence of various doses of CRH. CRH significantly increased IL-6 release from PBMC (p < 0.01). The addition of CRH to PBMC significantly decreased IFN-gamma levels, in a dose dependent manner (p < 0.01). No significant effect of CRH was observed on lymphocyte proliferation or IL-1 beta production. The present results suggest a role for CRH as a paracrine mediator for human immune cells, increasing the evidence of a clear correlation between immune and neuroendocrine system.
Adult↗
Stressful life events and affective disorders inhibit pulsatile LH secretion in hypothalamic amenorrhea.
The aim of this study was to evaluate relationships between emotional state and hypothalamic activity in patients with hypothalamic secondary amenorrhea. Sixty-seven normal weight patients with hypothalamic amenorrhea were submitted to concomitant psychological and LH pulsatility evaluation. Structured clinical interview for anxiety and depressive disorders (DSM III-R) as well as life events investigations (Paykel test) were performed. LH pulses (blood sampling every 10 min for 4 hr) were analyzed through DETECT program and Instantaneous Secretory Rate were computed. Twenty-one patients reporting life events associated to the onset of amenorrhea had LH pulse frequency (2.28 +/- 1.10 pulses/4 hr) lower than those without life events (3.40 +/- 1.46 p = .007). LH pulses amplitude was lower in patients meeting a DSM III-R (21 cases: 1.22 +/- 0.96 mIU/ml) diagnosis than in those without (1.99 +/- 1.20 p = .04) diagnosis. Plasma estradiol and FSH levels as well as duration of amenorrhea and Body Mass Index were similar among groups. It is concluded that psychogenic factors (namely the presence of life events related to the onset of menstrual disorder) are associated with significant and specific changes of hypothalamic activity which could be involved in determining hypogonadism.
Adult↗
Hormonal treatments modulate pulsatile plasma growth hormone, gonadotrophin and osteocalcin levels in postmenopausal women.
Oestrogen plays a role in modulating growth hormone (GH), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and osteocalcin secretion in women. Indeed, the postmenopausal period is characterized by changes in plasma GH, LH, FSH and osteocalcin levels. The aim of the present study was to investigate the changes in the secretory patterns of these hormones in postmenopausal women under different therapeutic regimens. A total of 20 subjects took part in the study. They were subdivided into four groups comprising 5 untreated postmenopausal women (time since menopause 1-5 years), 5 postmenopausal women receiving steroid hormone replacement therapy, 5 postmenopausal women receiving salmon calcitonin and 5 fertile women with regular menstrual cycles. Blood samples were collected every 15 min for 4 h and hormone levels were measured by radioimmunoassay. Plasma GH levels fell in the postmenopausal women, but were restored under oestrogen-progestogen treatment. The pulsatile patterns of plasma LH and FSH did not show significant differences in the treated and untreated women. Plasma osteocalcin levels showed episodic fluctuations and mean levels decreased under steroid hormone or calcitonin treatment. No significant correlation was observed between plasma GH and osteocalcin or gonadotrophin levels or body mass index.
Calcitonin↗
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.
Amenorrhea↗
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.
Endorphins↗
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.
Adult↗
Acetyl-L-carnitine effect on pituitary and plasma beta-endorphin responsiveness to different chronic intermittent stressors.
The aims of the present study were: 1) to compare the effect of two different chronic intermittent stressors i.e. cold-swimming versus ether, on the pituitary opioidergic system; 2) to evaluate the response of pituitary and plasma beta-endorphin (beta-EP) to an acute stress in chronically stressed rats; and 3) to evaluate the effect of acetyl-l-carnitine treatment (10 mg/day/rat per os at night) on pituitary and plasma beta-EP changes induced by two different types of chronic stress. The stressors were applied twice a day for 10 days. Rats were killed either before, during or after the last swimming or ether stress session. beta-EP was measured by radioimmunoassay in anterior pituitary and in neurointermediate lobe extracts and in plasma. The following observations were made: 1) Chronic intermittent cold-swimming stress increased anterior pituitary contents and plasma beta-EP levels; 2) both chronic intermittent cold-swimming stress and ether stress caused an increase of neurointermediate lobe beta-EP contents; 3) as in control animals, rats exposed to chronic intermittent swimming stress reduced pituitary beta-EP contents and raised plasma beta-EP levels in response to the last acute swimming stress; 4) in contrast to control animals, rats exposed to chronic intermittent ether stress did not show any significant response of the pituitary-plasma opioidergic system to the last acute ether session; 5) the acetyl-l-carnitine treatment counteracted the changes evoked by chronic intermittent cold-swimming stress on the pituitary and plasma beta-EP levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetylcarnitine↗