Effect of dopamine on gonadotropin-releasing hormone-induced gonadotropin secretion in postmenopausal women.

Five healthy women who had previously undergone spontaneous menopause and had not received exogenous estrogens were studied with infusions of synthetic GnRH and dopamine to ascertain the site of dopaminergic modulation of pituitary gonadotropin secretion. Infusion of dopamine at 4 micrograms/kg . min for 5 h induced a significant decrease in circulating LH concentrations, but not those of FSH. LH levels returned to baseline concentrations during the postinfusion period. Infusion with synthetic GnRH at 10 micrograms/h for 5 h induced a biphasic change in circulating gonadotropin levels. When dopamine and GnRH were simultaneously infused for 5 h, FSH and LH responses were not statistically different from those observed when GnRH was infused alone. We conclude that in normal postmenopausal women, dopamine modulates pituitary gonadotropin secretion by affecting GnRH-secreting neurons in the median eminence and possibly at other hypothalamic sites.

Characterization of a small molecular size urinary immunoreactive human chorionic gonadotropin (hCG)-like substance produced by normal placenta and by hCG-secreting neoplasms.

Urine obtained from normal pregnant women as well as from patients with hCG-secreting tumors frequently contains native hCG and free hCG subunits when separated on Sephadex G-100. In addition, a small amount of an immunoreactive, hCG-like, low molecular weight substance is usually observed in those chromatograms and represents less than 1% of the total immunoreactive hCG present. Two patients with widely metastatic hCG-secreting tumors excreted disproportionately large quantities of that low molecular weight substance, and that observation raised the possibility that this substance was a secretory and not a degradative product of the hCG molecule. The small immunoreactive hCG-like substance was subsequently characterized immunologically, biologically, and physically. The hCG fragment displayed a biphasic dose-response line in a homologous hCG RIA. The slope of the upper portion of the dose-response line was equal to that for native hCG, but the slope of the lower component of the dose-response line was significantly different from that for hCG. The immunoreactive hCG substance cross-reacted with hCG beta but not with either hCG alpha or hCG beta carboxyl-terminus. The small molecular size immunoreactive hCG-like substance bound to Concanavalin A-Sepharose 4B and eluted with 0.2 M alpha-D-methyl glucopyranoside, contained no significant intrinsic biological activity when tested in the in vitro Leydig cell bioassay and also failed to compete with labeled hCG for specific ovarian LH/hCG receptors. Consequently, that small urinary immunoreactive hCG substance behaved neither as a hCG agonist or antagonist. It exhibited a plasma half-life of 4.5 min when the appropriate Sephadex G-100 fractions were injected into immature female rats. The small molecular size immunoreactive hCG-like substance may be a secretory or breakdown product of hCG-secreting cells.