Pituitary and Gonadal Gonadotropin-Releasing Hormone Receptors during Sexual Maturation in the Rat*

Abstract

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

Evolution of Constrained Gonadotropin-releasing Hormone Ligand Conformation and Receptor Selectivity

“…The dilution of GnRH in the portal vessels may, thus, have driven the evolution of the more compact GnRH with higher affinity binding. However, some of the earlier-evolved functions seen in protochordates appear to have been retained in vertebrates as GnRH and GnRH receptors are present in the gonads of fish, amphibians, and mammals (5-7), suggesting direct effects on gonads (40).…”

Developmental changes in LH secretion by male pituitaries in vitro: from the infantile to adult period

“…On the other hand, Ojeda et al (1977) found that the infantile female rat is more sensitive to GnRH compared with the neonatal and juvenile rat. Dalkin et al (1981) observed a sharp peak in GnRH receptor density in the pituitaries of female infantile rats. However, during this development stage male pituitaries showed only a discrete increase in GnRH-binding capacity, and the largest receptor density was observed in 30-day-old rats (Dalkin et al 1981).…”

“…Dalkin et al (1981) observed a sharp peak in GnRH receptor density in the pituitaries of female infantile rats. However, during this development stage male pituitaries showed only a discrete increase in GnRH-binding capacity, and the largest receptor density was observed in 30-day-old rats (Dalkin et al 1981). Also, it has been shown that infantile male pituitary gonadotrope cells are heterogeneous, with a significant population of small cells (Denef et al 1978 as in the female pituitary (Denef et al 1978), and also they exhibit an irregular shape and a high nucleo-cytoplasmic ratio .…”

Role of GnRH in the maturation of pituitary gonadotroph function

“…This is paralleled closely by an increased pituitary LH content (Chan et al, 1981 (Chan et al, 1981;Dalkin et al, 1981). The decline in GnRH receptor concentration is mirrored by increasing serum testosterone concentrations, suggesting that an increased negative feedback action of gonadal hormones may cause a reduction in GnRH receptors either secondary to an inhibition of endogenous GnRH secretion (Chan et al, 1981) or by a direct inhibitory action of testosterone on the gonadotrophs (Giguere, Lefebvre & Labrie, 1981 (Döhler & Wuttke, 1975;Chan et al, 1981;Dalkin et al, 1981).…”

“…The decline in GnRH receptor concentration is mirrored by increasing serum testosterone concentrations, suggesting that an increased negative feedback action of gonadal hormones may cause a reduction in GnRH receptors either secondary to an inhibition of endogenous GnRH secretion (Chan et al, 1981) or by a direct inhibitory action of testosterone on the gonadotrophs (Giguere, Lefebvre & Labrie, 1981 (Döhler & Wuttke, 1975;Chan et al, 1981;Dalkin et al, 1981). The concentrations of serum FSH, as in male rats, rise characteristically between Days 10 and 20 of age with a peak value at Day 15 (Ojeda et al, 1980;Chan et al, 1981;Dalkin et al, 1981 (Debeljuk et al, 1972b;Ojeda, Jameson & McCann, 1977;Dullart, 1977 (Chan et al, 1981), since the latter remained constant after 30 days of age. Before this time high concentrations of a-fetoprotein in serum cause elevated total serum oestradiol concentrations in female rats.…”