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Gene Review

GNRH1  -  gonadotropin-releasing hormone 1...

Ovis aries

Synonyms: GNRH, LHRH
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Disease relevance of GNRH

  • Signaling and antiproliferative effects of type I and II gonadotropin-releasing hormone receptors in breast cancer cells [1].
  • These data indicate that neonatal immunization does not affect the synthesis of GnRH in adulthood but reduces the secretion of GnRH, causing long-term sterility in these animals [2].
  • Hypersensitivity (2-fold increase) to GnRH was briefly observed at the beginning of the period of E2beta-facilitated LH release [3].
  • Eighteen prepubertal lambs (21 weeks of age, 34.2 +/- 1.5 kg body weight) were treated intravenously with either NMA (2 mg/kg, n = 6) or GnRH (68 ng/injection or approximately 2 ng/kg, n = 6) for 3 days, every 2 h on day 1 and every 1 h on days 2 and 3, or received no treatment (controls, n = 6) [4].
  • Although application as a fertility control agent in men is unlikely, there is renewed interest in active immunization against GnRH as a means of treating prostate cancers and related steroid-dependent pathologies [5].

High impact information on GNRH


Biological context of GNRH


Anatomical context of GNRH

  • We conclude that gonadotropin release from the pituitary gland requires the continual presence of GnRH during the ascending limb of the preovulatory gonadotropin surge, and that once the surge has been triggered, the ovaries do not appear to be required for further hypothalamic stimulation [14].
  • There were no significant changes in the amount of GnRH contained in the preoptic area, the median eminence, or the hypothalamus [15].
  • In the Suffolk ewe, seasonal reproductive transitions are due primarily to changes in the responsiveness of the GnRH neurosecretory system to the negative feedback influence of estradiol [13].
  • When delivered to the anterior pituitary gland continuously, GnRH decreases numbers of GnRH receptors on gonadotropes [16].
  • Simultaneous measurement of gonadotropin-releasing hormone in the third ventricular cerebrospinal fluid and hypophyseal portal blood of the ewe [17].

Associations of GNRH with chemical compounds


Physical interactions of GNRH


Regulatory relationships of GNRH


Other interactions of GNRH


Analytical, diagnostic and therapeutic context of GNRH

  • The number of receptors for GnRH (GnRH-rec) can vary from 500 to 15,000-20,000/gonadotrope in ovine pituitary cultures after treatment with physiologically relevant combinations of gonadal hormones [28].
  • We suggest that Fos expression in GnRH cells is markedly increased by the positive feedback action of estradiol (surge), whereas short-term removal of negative feedback (ovariectomy) has little, if any, effect, despite increased GnRH release in both states [11].
  • Experiments were performed using an animal model in which GnRH secretion was blocked by progesterone, which in itself does not block the pituitary response to GnRH [29].
  • Further studies on the radioimmunoassay of gonadotropin-releasing hormone: effect of radioiodination, antiserum and unextracted serum on levels of immunoreactivity in serum [30].
  • Intact ewes treated with 100 micrograms GnRH also released an amount of LH similar to that in the control group [14].


  1. Signaling and antiproliferative effects of type I and II gonadotropin-releasing hormone receptors in breast cancer cells. Finch, A.R., Green, L., Hislop, J.N., Kelly, E., McArdle, C.A. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  2. Neonatal immunization against gonadotropin-releasing hormone (GnRH) results in diminished GnRH secretion in adulthood. Clarke, I.J., Brown, B.W., Tran, V.V., Scott, C.J., Fry, R., Millar, R.P., Rao, A. Endocrinology (1998) [Pubmed]
  3. Biphasic effect of estradiol on mechanisms regulating LH release in ovariectomized sheep. Coppings, R.J., Malven, P.V. Neuroendocrinology (1976) [Pubmed]
  4. Hypothalamic versus pituitary stimulation of luteinizing hormone secretion in the prepubertal female lamb. I'Anson, H., Herbosa, C.G., Ebling, F.J., Wood, R.I., Bucholtz, D.C., Mieher, C.D., Foster, D.L., Padmanabhan, V. Neuroendocrinology (1993) [Pubmed]
  5. Immunization against GnRH in male species (comparative aspects). Thompson, D.L. Anim. Reprod. Sci. (2000) [Pubmed]
  6. New insights regarding glucocorticoids, stress and gonadotropin suppression. Breen, K.M., Karsch, F.J. Frontiers in neuroendocrinology. (2006) [Pubmed]
  7. The negative feedback actions of progesterone on gonadotropin-releasing hormone secretion are transduced by the classical progesterone receptor. Skinner, D.C., Evans, N.P., Delaleu, B., Goodman, R.L., Bouchard, P., Caraty, A. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  8. Evidence for a two-step mechanism of gonadotropin-releasing hormone metabolism by prolyl endopeptidase and metalloendopeptidase EC in ovine hypothalamic extracts. Lew, R.A., Tetaz, T.J., Glucksman, M.J., Roberts, J.L., Smith, A.I. J. Biol. Chem. (1994) [Pubmed]
  9. Direct effects of luteal regression on anterior pituitary response to GNRH. McWilliams, D., Dunn, A.M., Esquivel, E., Wise, M.E. Domest. Anim. Endocrinol. (1998) [Pubmed]
  10. Does estradiol induce the preovulatory gonadotropin-releasing hormone (GnRH) surge in the ewe by inducing a progressive change in the mode of operation of the GnRH neurosecretory system. Evans, N.P., Dahl, G.E., Mauger, D.T., Padmanabhan, V., Thrun, L.A., Karsch, F.J. Endocrinology (1995) [Pubmed]
  11. Fos expression during the estradiol-induced gonadotropin-releasing hormone (GnRH) surge of the ewe: induction in GnRH and other neurons. Moenter, S.M., Karsch, F.J., Lehman, M.N. Endocrinology (1993) [Pubmed]
  12. Pattern of gonadotropin-releasing hormone (GnRH) secretion leading up to ovulation in the ewe: existence of a preovulatory GnRH surge. Moenter, S.M., Caraty, A., Locatelli, A., Karsch, F.J. Endocrinology (1991) [Pubmed]
  13. Evidence for seasonal plasticity in the gonadotropin-releasing hormone (GnRH) system of the ewe: changes in synaptic inputs onto GnRH neurons. Xiong, J.J., Karsch, F.J., Lehman, M.N. Endocrinology (1997) [Pubmed]
  14. Control of the preovulatory gonadotropin surge in the ewe. Webb, R., England, B.G., Fitzpatrick, K.E. Endocrinology (1981) [Pubmed]
  15. Pituitary content of gonadotropins and receptors for gonadotropin-releasing hormone (GnRH) and hypothalamic content of GnRH during the periovulatory period of the ewe. Crowder, M.E., Nett, T.M. Endocrinology (1984) [Pubmed]
  16. Regulation of gonadotropin-releasing hormone (GnRH) receptor gene expression in sheep: interaction of GnRH and estradiol. Turzillo, A.M., Nolan, T.E., Nett, T.M. Endocrinology (1998) [Pubmed]
  17. Simultaneous measurement of gonadotropin-releasing hormone in the third ventricular cerebrospinal fluid and hypophyseal portal blood of the ewe. Skinner, D.C., Caraty, A., Malpaux, B., Evans, N.P. Endocrinology (1997) [Pubmed]
  18. Central regulation of pulsatile gonadotropin-releasing hormone (GnRH) secretion by estradiol during the period leading up to the preovulatory GnRH surge in the ewe. Evans, N.P., Dahl, G.E., Glover, B.H., Karsch, F.J. Endocrinology (1994) [Pubmed]
  19. A gamma-aminobutyric acidB agonist reverses the negative feedback effect of testosterone on gonadotropin-releasing hormone and luteinizing hormone secretion in the male sheep. Jackson, G.L., Wood, S.G., Kuehl, D.E. Endocrinology (2000) [Pubmed]
  20. Effects of epinephrine, norepinephrine, and dopamine on gonadotropin-releasing hormone-induced secretion of luteinizing hormone in vitro. Swartz, S.R., Moberg, G.P. Endocrinology (1986) [Pubmed]
  21. Estradiol and gonadotropin-releasing hormone (GnRH) interact to increase GnRH receptor expression in ovariectomized ewes after hypothalamic-pituitary disconnection. Kirkpatrick, B.L., Esquivel, E., Moss, G.E., Hamernik, D.L., Wise, M.E. Endocrine (1998) [Pubmed]
  22. Extracellular signal-regulated kinase, Jun N-terminal kinase, p38, and c-Src are involved in gonadotropin-releasing hormone-stimulated activity of the glycoprotein hormone follicle-stimulating hormone beta-subunit promoter. Bonfil, D., Chuderland, D., Kraus, S., Shahbazian, D., Friedberg, I., Seger, R., Naor, Z. Endocrinology (2004) [Pubmed]
  23. Does the type II glucocorticoid receptor mediate cortisol-induced suppression in pituitary responsiveness to gonadotropin-releasing hormone? Breen, K.M., Stackpole, C.A., Clarke, I.J., Pytiak, A.V., Tilbrook, A.J., Wagenmaker, E.R., Young, E.A., Karsch, F.J. Endocrinology (2004) [Pubmed]
  24. Thyroid hormone receptor (alpha) distribution in hamster and sheep brain: colocalization in gonadotropin-releasing hormone and other identified neurons. Jansen, H.T., Lubbers, L.S., Macchia, E., DeGroot, L.J., Lehman, M.N. Endocrinology (1997) [Pubmed]
  25. Are immediate early genes involved in gonadotropin-releasing hormone receptor gene regulation? Characterization of changes in GnRH receptor (GnRH-R), c-fos, and c-jun messenger ribonucleic acids during the ovine estrous cycle. Padmanabhan, V., Dalkin, A., Yasin, M., Haisenleder, D.J., Marshall, J.C., Landefeld, T.D. Biol. Reprod. (1995) [Pubmed]
  26. Stimulating effect of glycoprotein hormone free alpha-subunit and daily gonadotropin releasing hormone treatment on prolactin release from 50-day ovine foetal pituitary explants. Chabot, V., Gauthier, C., Combarnous, Y., Taragnat, C. J. Neuroendocrinol. (2001) [Pubmed]
  27. Regulation of gonadotropin releasing hormone release by neuropeptide Y at the median eminence during the preovulatory period in ewes. Advis, J.P., Klein, J., Kuljis, R.O., Sarkar, D.K., McDonald, J.M., Conover, C.A. Neuroendocrinology (2003) [Pubmed]
  28. Gonadal hormones and gonadotropin-releasing hormone (GnRH) alter messenger ribonucleic acid levels for GnRH receptors in sheep. Wu, J.C., Sealfon, S.C., Miller, W.L. Endocrinology (1994) [Pubmed]
  29. Importance of the gonadotropin-releasing hormone (GnRH) surge for induction of the preovulatory luteinizing hormone surge of the ewe: dose-response relationship and excess of GnRH. Bowen, J.M., Dahl, G.E., Evans, N.P., Thrun, L.A., Wang, Y., Brown, M.B., Karsch, F.J. Endocrinology (1998) [Pubmed]
  30. Further studies on the radioimmunoassay of gonadotropin-releasing hormone: effect of radioiodination, antiserum and unextracted serum on levels of immunoreactivity in serum. Nett, T.M., Adams, T.E. Endocrinology (1977) [Pubmed]
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