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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1986 Jun;83(11):4026–4029. doi: 10.1073/pnas.83.11.4026

Gonadotropin-releasing hormone differentially regulates expression of the genes for luteinizing hormone alpha and beta subunits in male rats.

S S Papavasiliou, S Zmeili, S Khoury, T D Landefeld, W W Chin, J C Marshall
PMCID: PMC323658  PMID: 3012543

Abstract

Gonadotropin-releasing hormone (GnRH) and gonadal steroids regulate synthesis and release of luteinizing hormone (LH). GnRH is secreted intermittently by the hypothalamus, producing pulsatile LH release, and a pulsatile GnRH stimulus is required to maintain LH secretion. We report the regulatory effects of GnRH pulse injections on pituitary concentrations of LH alpha and beta subunit mRNAs in a castrated/testosterone-replaced male rat model. Replacement with physiologic amounts of testosterone decreased concentrations of both LH subunit mRNAs. GnRH pulse injections (10-250 ng per pulse given every 30 min for 48 hr) increased both mRNA concentrations, but the dose response patterns were markedly different. alpha subunit mRNA was increased by all GnRH doses but not the levels seen after castration alone. In contrast, LH beta subunit mRNA concentrations showed a marked dependence on GnRH dose. Maximal responses, to values similar to those in castrates, occurred after 25-ng GnRH pulses, and larger doses produced a smaller increase in LH beta subunit mRNA. Both the acute LH secretory response to GnRH and the number of GnRH receptors followed a pattern similar to the LH beta subunit mRNA concentration and were maximal after the 25-ng GnRH dose. These results show that GnRH can differentially regulate LH subunit mRNAs and suggest that concentrations of LH beta subunit mRNA may be a limiting factor in GnRH-stimulated LH release.

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Selected References

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  1. Baird D. T. Pulsatile secretion of LH and ovarian estradiol during the follicular phase of the sheep estrous cycle. Biol Reprod. 1978 Apr;18(3):359–364. doi: 10.1095/biolreprod18.3.359. [DOI] [PubMed] [Google Scholar]
  2. Birnboim H. C., Doly J. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 1979 Nov 24;7(6):1513–1523. doi: 10.1093/nar/7.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chan V., Clayton R. N., Knox G., Catt K. J. Ontogeny of pituitary GnRH receptors in the rat. Endocrinology. 1981 Jun;108(6):2086–2092. doi: 10.1210/endo-108-6-2086. [DOI] [PubMed] [Google Scholar]
  4. Charlton H. M., Halpin D. M., Iddon C., Rosie R., Levy G., McDowell I. F., Megson A., Morris J. F., Bramwell A., Speight A. The effects of daily administration of single and multiple injections of gonadotropin-releasing hormone on pituitary and gonadal function in the hypogonadal (hpg) mouse. Endocrinology. 1983 Aug;113(2):535–544. doi: 10.1210/endo-113-2-535. [DOI] [PubMed] [Google Scholar]
  5. Chin W. W., Godine J. E., Klein D. R., Chang A. S., Tan L. K., Habener J. F. Nucleotide sequence of the cDNA encoding the precursor of the beta subunit of rat lutropin. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4649–4653. doi: 10.1073/pnas.80.15.4649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Clarke I. J., Cummins J. T. The temporal relationship between gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) secretion in ovariectomized ewes. Endocrinology. 1982 Nov;111(5):1737–1739. doi: 10.1210/endo-111-5-1737. [DOI] [PubMed] [Google Scholar]
  7. Clayton R. N. Gonadotropin-releasing hormone modulation of its own pituitary receptors: evidence for biphasic regulation. Endocrinology. 1982 Jul;111(1):152–161. doi: 10.1210/endo-111-1-152. [DOI] [PubMed] [Google Scholar]
  8. Clayton R. N., Shakespear R. A., Duncan J. A., Marshall J. C. Luteinizing hormone-releasing hormone inactivation by purified pituitary plasma membranes: effects of receptor-binding studies. Endocrinology. 1979 May;104(5):1484–1494. doi: 10.1210/endo-104-5-1484. [DOI] [PubMed] [Google Scholar]
  9. Clayton R. N., Solano A. R., Garcia-Vela A., Dufau M. L., Catt K. J. Regulation of pituitary receptors for gonadotropin-releasing hormone during the rat estrous cycle. Endocrinology. 1980 Sep;107(3):699–706. doi: 10.1210/endo-107-3-699. [DOI] [PubMed] [Google Scholar]
  10. Conn P. M., Chafouleas J. G., Rogers D., Means A. R. Gonadotropin releasing hormone stimulates calmodulin redistribution in rat pituitary. Nature. 1981 Jul 16;292(5820):264–265. doi: 10.1038/292264a0. [DOI] [PubMed] [Google Scholar]
  11. Conn P. M., Rogers D. C., Sheffield T. Inhibition of gonadotropin-releasing hormone-stimulated luteinizing hormone release by pimozide: evidence for a site of action after calcium mobilization. Endocrinology. 1981 Oct;109(4):1122–1126. doi: 10.1210/endo-109-4-1122. [DOI] [PubMed] [Google Scholar]
  12. Corbani M., Counis R., Starzec A., Jutisz M. Effect of gonadectomy on pituitary levels of mRNA encoding gonadotropin subunits and secretion of luteinizing hormone. Mol Cell Endocrinol. 1984 May;35(2-3):83–87. doi: 10.1016/0303-7207(84)90003-0. [DOI] [PubMed] [Google Scholar]
  13. Corbani M., Counis R., Starzec A., Jutisz M. Effect of gonadectomy on pituitary levels of mRNA encoding gonadotropin subunits and secretion of luteinizing hormone. Mol Cell Endocrinol. 1984 May;35(2-3):83–87. doi: 10.1016/0303-7207(84)90003-0. [DOI] [PubMed] [Google Scholar]
  14. Dalkin A. C., Bourne G. A., Pieper D. R., Regiani S., Marshall J. C. Pituitary and gonadal gonadotropin-releasing hormone receptors during sexual maturation in the rat. Endocrinology. 1981 May;108(5):1658–1664. doi: 10.1210/endo-108-5-1658. [DOI] [PubMed] [Google Scholar]
  15. Davies T. F., Gomez-Pan A., Watson M. J., Mountjoy C. Q., Hanker J. P., Besser G. M., Hall R. Reduced 'gonadotrophin response to releasing hormone' after chronic administration to impotent men. Clin Endocrinol (Oxf) 1977 Mar;6(3):213–218. doi: 10.1111/j.1365-2265.1977.tb03317.x. [DOI] [PubMed] [Google Scholar]
  16. Gallo R. V. Pulsatile LH release during periods of low level LH secretion in the rat estrous cycle. Biol Reprod. 1981 May;24(4):771–777. doi: 10.1095/biolreprod24.4.771. [DOI] [PubMed] [Google Scholar]
  17. Gallo R. V. Pulsatile LH release during the ovulatory LH surge on proestrus in the rat. Biol Reprod. 1981 Feb;24(1):100–104. doi: 10.1095/biolreprod24.1.100. [DOI] [PubMed] [Google Scholar]
  18. Garcia A., Schiff M., Marshall J. C. Regulation of pituitary gonadotropin-releasing hormone receptors by pulsatile gonadotropin-releasing hormone injections in male rats. Modulation by testosterone. J Clin Invest. 1984 Sep;74(3):920–928. doi: 10.1172/JCI111510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gay V. L., Sheth N. A. Evidence for a periodic release of LH in castrated male and female rats. Endocrinology. 1972 Jan;90(1):158–162. doi: 10.1210/endo-90-1-158. [DOI] [PubMed] [Google Scholar]
  20. Godine J. E., Chin W. W., Habener J. F. alpha Subunit of rat pituitary glycoprotein hormones. Primary structure of the precursor determined from the nucleotide sequence of cloned cDNAs. J Biol Chem. 1982 Jul 25;257(14):8368–8371. [PubMed] [Google Scholar]
  21. Hoshina H., Boime I. Combination of rat lutropin subunits occurs early in the secretory pathway. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7649–7653. doi: 10.1073/pnas.79.24.7649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Katt J. A., Duncan J. A., Herbon L., Barkan A., Marshall J. C. The frequency of gonadotropin-releasing hormone stimulation determines the number of pituitary gonadotropin-releasing hormone receptors. Endocrinology. 1985 May;116(5):2113–2115. doi: 10.1210/endo-116-5-2113. [DOI] [PubMed] [Google Scholar]
  23. Labarca C., Paigen K. A simple, rapid, and sensitive DNA assay procedure. Anal Biochem. 1980 Mar 1;102(2):344–352. doi: 10.1016/0003-2697(80)90165-7. [DOI] [PubMed] [Google Scholar]
  24. Nankin H. R., Troen P. Repetitive luteinizing hormone elevations in serum of normal men. J Clin Endocrinol Metab. 1971 Sep;33(3):558–560. doi: 10.1210/jcem-33-3-558. [DOI] [PubMed] [Google Scholar]
  25. Nilson J. H., Nejedlik M. T., Virgin J. B., Crowder M. E., Nett T. M. Expression of alpha subunit and luteinizing hormone beta genes in the ovine anterior pituitary. Estradiol suppresses accumulation of mRNAS for both alpha subunit and luteinizing hormone beta. J Biol Chem. 1983 Oct 25;258(20):12087–12090. [PubMed] [Google Scholar]
  26. Reame N., Sauder S. E., Kelch R. P., Marshall J. C. Pulsatile gonadotropin secretion during the human menstrual cycle: evidence for altered frequency of gonadotropin-releasing hormone secretion. J Clin Endocrinol Metab. 1984 Aug;59(2):328–337. doi: 10.1210/jcem-59-2-328. [DOI] [PubMed] [Google Scholar]
  27. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  28. Sandow J., von Rechenberg W., Kuhl H., Baumann R., Krauss B., Jerzabek G., Kille S. Inhibitory control of the pituitary LH secretion by LH-RH in male rats. Horm Res. 1979;11(6):303–317. doi: 10.1159/000179068. [DOI] [PubMed] [Google Scholar]
  29. Savoy-Moore R. T., Schwartz N. B., Duncan J. A., Marshall J. C. Pituitary gonadotropin-releasing hormone receptors during the rat estrous cycle. Science. 1980 Aug 22;209(4459):942–944. doi: 10.1126/science.6250218. [DOI] [PubMed] [Google Scholar]
  30. Steiner R. A., Bremner W. J., Clifton D. K. Regulation of luteinizing hormone pulse frequency and amplitude by testosterone in the adult male rat. Endocrinology. 1982 Dec;111(6):2055–2061. doi: 10.1210/endo-111-6-2055. [DOI] [PubMed] [Google Scholar]
  31. Steiner R. A., Peterson A. P., Yu J. Y., Conner H., Gilbert M., terPenning B., Bremner W. J. Ultradian luteinizing hormone and testosterone rhythms in the adult male monkey, Macaca fascicularis. Endocrinology. 1980 Nov;107(5):1489–1493. doi: 10.1210/endo-107-5-1489. [DOI] [PubMed] [Google Scholar]
  32. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Valk T. W., Corley K. P., Kelch R. P., Marshall J. C. Hypogonadotropic hypogonadism: hormonal responses to low dose pulsatile administration of gonadotropin-releasing hormone. J Clin Endocrinol Metab. 1980 Oct;51(4):730–738. doi: 10.1210/jcem-51-4-730. [DOI] [PubMed] [Google Scholar]
  34. White B. A., Bancroft F. C. Cytoplasmic dot hybridization. Simple analysis of relative mRNA levels in multiple small cell or tissue samples. J Biol Chem. 1982 Aug 10;257(15):8569–8572. [PubMed] [Google Scholar]

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