Dynamics of basal and gonadotropin-releasing hormone-releasable serum follicle-stimulating hormone charge isoform distribution throughout the human menstrual cycle.

Abstract

In the present study we analyzed physiological changes in the relative distribution of FSH isoforms circulating under baseline conditions throughout the ovarian cycle as well as the forms discharged by GnRH stimulation from putative acutely releasable and reserve pituitary pools. Eight normally menstruating women underwent blood sampling on three occasions, once each during the presumptive early or midfollicular phase (FP), late follicular phase to midcycle (preovulatory phase; PO), and mid- to late luteal phase (LP) of the menstrual cycle. Blood samples were withdrawn at 10-min intervals for a total of 10 h before and after the iv administration of 10 and 90 micrograms GnRH. GnRH-stimulated FSH pulses were analyzed for secretory burst mass, secretory burst amplitude, integrated FSH concentrations, and endogenous FSH half-life by deconvolution. Serum FSH isoforms were separated by preparative chromatofocusing in 30 x 1-cm columns and identified by RIA of eluent fractions. The changes observed in serum FSH isoform distribution were then correlated with the corresponding secretory and clearance estimates of the released FSH molecules. In each phase of the menstrual cycle, a significant rise in serum FSH concentrations was observed after administration of the consecutive low and high dose GnRH pulses. The magnitude of the response in terms of secretory burst mass, secretory amplitude, and area of GnRH-induced FSH peaks was significantly higher during the PO. In all cycle phases, but particularly during the FP and PO, administration of the 90-micrograms GnRH dose elicited higher (1.4- to 1.7-fold) FSH secretory responses than the lower dose. Multiple parameter deconvolution of the GnRH-induced FSH pulses revealed that FSH molecules released in response to 10 micrograms GnRH at PO exhibited significantly (P < 0.01) shorter plasma half-lives (108 +/- 11 min) than those released during the follicular and luteal phases of the same menstrual cycles (apparent plasma half-life of FSH released at FP, 222 +/- 37 and 271 +/- 47 min for 10 and 90 micrograms GnRH-induced FSH pulses, respectively; LP, 244 +/- 41 and 198 +/- 40 min; P = NS, FP vs. LP) and in response to the high dose GnRH challenge at PO (276 +/- 40 min). Under all conditions studied, serum FSH charge isoforms were distributed along a pH range of 7.0 to less than 4.0.(ABSTRACT TRUNCATED AT 400 WORDS)

A Naturally Occurring Basically Charged Human Follicle-Stimulating Hormone (FSH) Variant Inhibits FSH-Induced Androgen Aromatization and Tissue-Type Plasminogen Activator Enzyme Activity in vitro

“…the preovulatory phase of the menstrual cycle) this natural antihormone may function as a fine-tuning regulator of the intensity of the gonadotropic signal to avoid overstimulation of the growing follicle. In fact, we and others have found that the basal secretion of this particular FSH variant increases during the late follicular phase of the menstrual cycle [3, 11]. Conversely, abnormally elevated levels of this FSHi may counteract in excess the physiological gonadotropic stimulus and eventually lead to a hypogonadotropic state; this possibility is exemplified by the recently reported case of a young women with normal ovulatory menstrual cycles, infertility and low B/I FSH ratios [10]; 65% of her serum FSH eluted in a pH range above 6.0 and, in terms of estradiol production in vitro, had compromised bioactivity.…”

“…In the rat assay, the in vitro biopotency of this isoform was intermediate between those of the less and more acidic analogs whereas in the human assay it exhibited the highest in vitro biopotency [8]. The present study was conducted to further characterize the biological properties of this particular isoform which has been detected in abnormally high concentrations in some hypogonadal women [9, 10] and whose relative abundance in the circulation changes throughout the normal menstrual cycle [3, 11]. Since this isoform coelutes with extremely high quantities of luteinizing hormone (LH) in the CF procedure employed to fractionate the different FSH isoforms (fig.…”

Follicle-Stimulating Isohormones: Characterization and Physiological Relevance

“…Furthermore, char-acterization of rat, ovine, monkey, and human FSH isoforms secreted in vitro under different experimental conditions has shown that almost all stored FSH isoforms can be released from pituitary cells with few or no modifications in their number and pi values (29-31,40) and that sex differences in the distribution profile of FSH isoforms in donor pituitary extracts are retained in culture for both basal and GnRHstimulated release (29). Serum isoforms may be even more acidic than the intrapituitary analogs, particularly when they are isolated from specimens during unstimulated conditions (67,70); this apparent dis- , and zone electrophoresis (c). 2).…”

In vitro biological-to-immunological ratio of serum gonadotropins throughout male puberty in children with insulin-dependent diabetes mellitus

“…In fact, measurement of the B:I gonadotropin ratio has been shown to be an useful parameter to detect changes in the mixture of circulating isoforms that occur in several conditions, including puberty [16,17,36], the menstrual cycle [7,[37][38][39], and senescence [40,41], which are characterized by striking changes in sex steroid hormones and GnRH output.…”

“…In LH and FSH, carbohydrates play a major role in structure and function since they influence not only intracellular subunit folding and secretion of the heterodimer, but also its circulatory survival, receptor binding, and capacity to evoke signal transduction at the receptor level [5,6]. The number and relative abundance of these isoforms will depend on the endocrine status of the donor at the time of collection of the tissue or sample [5][6][7][8][9][10].…”