Estradiol potentiation of gonadotropin-releasing hormone responsiveness in the anterior pituitary is mediated by an increase in gonadotropin-releasing hormone receptors.
In order to investigate the mechanism by which 17 beta-estradiol potentiates the action of gonadotropin-releasing hormone on the anterior pituitary in vitro, cultured pituitary cells from immature female rats were used as the model system. Cultures exposed to estradiol at concentrations ranging from 10(-10) to 10(-6) mol/L exhibited a significant augmentation of luteinizing hormone release in response to a 4-hour gonadotropin-releasing hormone (10 mumol/L) challenge at a dose of 10(-9) mol/L compared to that of control cultures. The estradiol augmentation of luteinizing hormone release was also dependent on the duration of estradiol exposure. When these cultures were incubated with tritium-labeled L-leucine, an increase in incorporation of radiolabeled amino acid into total proteins greater than that in controls was observed. A parallel stimulatory effect of estradiol on iodine 125-labeled D-Ala6 gonadotropin-releasing hormone binding was observed. Cultures incubated with estradiol at different concentrations and various lengths of time showed a significant increase in gonadotropin-releasing hormone binding capacity and this increase was abrogated by cycloheximide. Analysis of the binding data showed that the increase in gonadotropin-releasing hormone binding activity was due to a change in the number of gonadotropin-releasing hormone binding sites rather than a change in the affinity. These results suggest that (1) estradiol treatment increases the number of pituitary receptors for gonadotropin-releasing hormone, (2) the augmentary effect of estradiol on luteinizing hormone release at the pituitary level might be mediated, at least in part, by the increase in the number of binding sites of gonadotropin-releasing hormone, and (3) new protein synthesis may be involved in estradiol-mediated gonadotropin-releasing hormone receptor induction.
Menon
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M
Peegel
H
H
Katta
V
V
D000818:Animals; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007457:Iodine Radioisotopes; D007930:Leucine / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D010906:Pituitary Hormone-Releasing Hormones / Q000378:metabolism*; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D011966:Receptors, LHRH; D013997:Time Factors; D014316:Tritium
D007457:Iodine Radioisotopes; D010906:Pituitary Hormone-Releasing Hormones; D011956:Receptors, Cell Surface; D011966:Receptors, LHRH; D014316:Tritium; D004958:Estradiol; D007986:Luteinizing Hormone; D003513:Cycloheximide; D007930:Leucine