Mode of pulsatile follicle-stimulating hormone secretion in gonadal hormone-sufficient and -deficient women--a clinical research center study.

To test the hypothesis that FSH is secreted at least in part within discrete secretory bursts in women and that the characteristics of episodic FSH secretion are altered within differing gonadal hormone environments, we measured FSH by immunoradiometric assay every 10 min for 24 h in premenopausal women during the early follicular (EF), late follicular (LF), and midluteal (ML) phases of the menstrual cycle and in postmenopausal (PM) women (n = 8 in each group). Secretory events were evaluated using multiparameter deconvolution. FSH was secreted in an episodic manner, with the number of secretory bursts (per 24 h; mean +/- SEM) detected in LF (20 +/- 0.79) and PM (20 +/- 0.90) women being greater than that in EF (16 +/- 0.88) and ML (14 +/- 0.93) women. FSH secretory burst mass (milliinternational units per mL) was significantly higher in PM (12 +/- 1.6) than in EF (1.8 +/- 0.21), LF (3.1 +/- 1.3), or ML (0.8 +/- 0.11) women and primarily reflected a relative increase in the maximal secretory rate rather than increased burst half-duration. The estimated half-life (minutes) of endogenous FSH in LF women (155 +/- 18) was shorter than those calculated in EF (251 +/- 24), ML (277 +/- 38), and PM (231 +/- 18) women. Cross-correlation analysis showed strongly positive associations between successively paired serum FSH and LH concentrations in all four groups of women. Deconvolution of simultaneously obtained LH concentration-time series revealed statistically significant concordance (13-25%) between FSH and LH secretory episodes at a lag time of 0 min in EF, LF, and PM women and when LH secretory bursts led FSH secretory bursts by 10 min in ML phase women. However, as 75-87% of FSH and LH secretory pulses were discordant, we infer the operation of distinct control mechanisms in the generation of FSH and LH release episodes. In summary, these results suggest that FSH is secreted within discrete secretory bursts in women, that the mass and frequency of FSH secretory bursts differ in women exhibiting various gonadal hormone environments, and that FSH and LH secretory bursts occur coincidentally at a higher rate than expected on the basis of chance alone, but at such a low overall rate of concordance that distinct mechanisms probably operate to direct episodic FSH and LH secretory activity.

Normal reproductive neuroendocrinology in the female.

The reproductive axis in women comprises a number of components that must function in a highly orchestrated manner for reproductive potential to be optimal. The neuroendocrine components of this axis, including the hypothalamus and the pituitary gland, are central to this system. Within the hypothalamus, the specialized neuronal system responsible for synthesizing and secreting gonadotropin-releasing hormone (GnRH) is itself modulated by a number of peptide and biogenic amine neurotransmitters that mediate feedback signals of ovarian origin. The luteinizing hormone and follicle-stimulating hormone secreting anterior pituitary gonadotropes perceive and transduce neural input in the form of GnRH, but are themselves also modulated by the ambient gonadal hormone concentrations. The authors review the physiologic relevance of the pulsatile nature of the GnRH signal, and some proposed mechanisms through which these signals are stimulated and modulated and subsequently perceived and transduced by gonadotropes.

Insulin-dependent diabetes mellitus and menstrual dysfunction.

Disordered reproductive function has long been recognized as a prevalent problem among women of reproductive age who suffer from insulin-dependent diabetes mellitus (IDDM). Delay in menarchial age is frequently seen if IDDM develops in the peripubertal years and some form of menstrual dysfunction is found in nearly one-third of all women of reproductive age with IDDM. This review summarizes some of the prevailing views regarding the mechanisms through which uncontrolled IDDM is thought to disrupt normal hypothalamic-pituitary-gonadal function. Although animal studies have suggested that poorly controlled IDDM may adversely affect the uterovaginal outflow tract and/or ovarian function, no clinical studies have suggested that abnormal uterine or ovarian function underlies the menstrual dysfunction observed in young diabetic women. Similarly, pituitary function as assessed by basal gonadotrophins and gonadotrophin-releasing hormone (GnRH)-stimulated gonadotrophin release appears to be normal in young women with IDDM. Moreover, although there has been some suggestion that pituitary function may decline with increasing duration of diabetes, this issue has not been thoroughly investigated. It appears that the oligo/amenorrhea noted in IDDM is principally hypothalamic in origin and may represent intermittent (and perhaps reversible) failure of the GnRH pulse generator, similar to the situation observed in women who engage in endurance training or who suffer from anorexia nervosa. Although the exact pathophysiological mechanisms that subserve dysfunction of the GnRH neuronal system are not well understood, attention has focused on increased central opioidergic activity, increased central dopaminergic activity, and central glucose deprivation. In this era of emphasis on tight glycaemic control and its impact in preventing diabetes complications, the consequences of IDDM on reproductive potential appear to be important and must be included in future investigative efforts.