A B S T R A C T To study the role of gonadotropin-releasing hormone (GnRH)

Gonadotropin-releasing hormone (GnRH) and its analogs have direct extrapituitary effects on the gonads to inhibit steroidogenesis. In the present study, the nondegradable GnRH analog [ 125 I]D-Ala a -des-Glyio-GnRH ethylamide is shown to specifically bind to ovarian, testicular, and adrenal membrane preparations. The ovarian GnRH receptor has a binding affinity similar to that of the anterior pituitary receptor and is specific for GnRH and GnRH analogs.The GnRH-binding capacity of whole ovarian membrane preparations is 150 fm/mg protein, 3-to 4-fold lower than that of anterior pituitary membranes. The number or affinity of receptors prepared from whole ovarian tissue is not influenced by the time of day, stage of the estrous cycle, or hypophysectomy. However, the GnRH receptor concentration is higher in follicular (371 ± 43 fmol/mg) than luteal (162 ± 25 fmol/mg) membranes from cycling rats.

The gonadotropin-releasing hormone (GnRH) agonist D-Ala 6 -des-Glyio-GnRH ethylamide (D-Ala analog) was used as ligand to study GnRH receptors in the pituitary and gonads during sexual maturation in the rat. The affinities of the GnRH receptor (Ka = 6.5 x 10 9 M" 1 ) were similar in all three tissues and did not change during maturation. Pituitary GnRH receptor concentration increased 2-fold in both sexes. Peak values occurred earlier (20 days) and were higher (720 ± 52 fmol/ mg protein) in females than in males (30 days; 594 ± 54 fmol/ mg). The changes in GnRH receptors followed a pattern similar to that of plasma FSH, though GnRH receptors were maximal 10 days after the FSH peak. The binding capacity of the gonadal GnRH receptors also changed with age, and was maximal on day 20 in females (271 ± 25 fmol/mg) before declining to a constant level by day 60 (139 ± 20 fmol/mg). In males, binding to testicular interstitial tissue was not detectable at 30 days of age but increased rapidly to 256 ± 13 fmol/mg by 40 days, before declining to a stable level at 60 days (160 ± 14 fm/mg). The parallel rise in plasma FSH and pituitary GnRH receptor concentrations suggest that both are mediated by increased hypothalamic secretion of GnRH. The highest concentrations of GnRH receptors in the pituitary was found at an age when pituitary responsiveness to GnRH is known to be maximal. This suggests that an increase in GnRH receptor numbers form an important part of the mechanisms involved in increasing pituitary responses to GnRH. While the factors involved in determining gonadal GnRH receptors are unknown, the observed changes in receptor concentration suggest that GnRH or a GnRH-like peptide may be involved in controlling steroidogenesis during sexual maturation. (Endocrinology 108: 1658, 1981) M ATURATIONAL changes in the hypothalamicpituitary axis resulting in increased gonadotropin-releasing hormone (GnRH) secretion are generally believed to be responsible for initiating sexual maturation in mammals. The exact mechanisms involved are complex and incompletely understood, but several facets of this process have been previously studied. Hypothalamic GnRH content increases steadily during the first 50-60 days of life (1-3). The pituitary content of LH and FSH also increases with age, though the time course is different between the sexes (4-7). The patterns of plasma LH, FSH, PRL, and gonadal steroid concentrations during sexual maturation in rats have also been documented in previous studies (8-15). In males, plasma FSH levels increase markedly to a peak at 30 days of age, whereas LH levels show little change but tend to increase gradually after 30 days. Plasma testosterone rises after 40 days of age (12, 16), the earlier exposure of the testis to FSH having enhanced testicular responsiveness to LH (17). In

This study confirms two factors about menopausal hormonal migraine: (1) it can be precipitated by a drop in serum estrogen levels, and (2) a period of estrogen priming is a necessary prerequisite. This study also identifies that there are two biologically different populations of postmenopausal women: (1) those who developed migraine after a single depo-estradiol injection, and (2) those who did not. By understanding that in addition to the biological predisposition to migraine there exists the biochemical cofactor of falling estrogen levels, we may better understand this phenomenon and develop means to prevent its occurrence.

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