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Molecular Pharmacology

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Research ArticleArticle

Regulation of the Rat Pituitary Gonadotropin-Releasing Hormone Receptor

JAN MARIAN, RALPH L. COOPER and P. MICHAEL CONN
Molecular Pharmacology May 1981, 19 (3) 399-405;
JAN MARIAN
Department of Pharmacology and Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, North Carolina 27710
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RALPH L. COOPER
Department of Pharmacology and Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, North Carolina 27710
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P. MICHAEL CONN
Department of Pharmacology and Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, North Carolina 27710
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Abstract

It is apparent that pituitary gonadotropin release changes quantitatively during various endocrine states, such as those found during ovarian cyclicity, lactation, aging, and ovariectomy. In the present work, we have used a radioligand prepared from a nondegradable, superagonist of gonadotropin-releasing hormone (GnRH) to determine the number and binding affinity of GnRH receptors during these endocrine states. While receptor affinity was unaltered (range 1.6-2.7 x 1O10 M-1), marked differences were observed in the receptor number throughout the estrous cycle [maximal in late diestrus II and proestrus immediately preceding the luteinizing hormone (LH) spike]. Lactating animals and old animals also had diminished concentrations (number per milligram of protein) of GnRH receptors as compared with young precycling females. Ovariectomy increased the number of receptors, and injections of estradiol benzoate to ovariectomized animals reversed this increase within 3 hr. Throughout the study, elevated receptor numbers were generally associated with elevated LH levels, although this alone did not appear to be sufficient for increased LH secretion. The present results suggest that regulation of the GnRH receptor may be one mechanism through which gonadotrope sensitivity is regulated.

ACKNOWLEDGMENT We thank Dr. C. Powell-Jones for suggesting the utility of the electrophoresis system described above. Note added in proof. Since acceptance of the manuscript, another report has been published (26) which indicates that castration of adult rats results in a 2-fold increase in GnRH binding capacity of the pituitary within 7 days. As shown in the present study, this effect is reversed by steroid administration. These authors have indicated that administration of rabbit antiserum, prepared against GnRH, concomitant with castration, inhibits the rise in both GnRH receptor number and LH increase. They have shown that changes in pituitary GnRH receptors parallel previously demonstrated changes in hypothalamic secretion of GnRH. The authors have suggested that GnRH probably regulates its own receptor in vivo and that gonadal steroids may influence pituitary GnRH receptors by changing hypothalamic GnRH secretion.

  • Copyright © 1981 by The American Society for Pharmacology and Experimental Therapeutics

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Molecular Pharmacology
Vol. 19, Issue 3
1 May 1981
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Research ArticleArticle

Regulation of the Rat Pituitary Gonadotropin-Releasing Hormone Receptor

JAN MARIAN, RALPH L. COOPER and P. MICHAEL CONN
Molecular Pharmacology May 1, 1981, 19 (3) 399-405;

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Research ArticleArticle

Regulation of the Rat Pituitary Gonadotropin-Releasing Hormone Receptor

JAN MARIAN, RALPH L. COOPER and P. MICHAEL CONN
Molecular Pharmacology May 1, 1981, 19 (3) 399-405;
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