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Gene Review

GNRH1  -  gonadotropin-releasing hormone 1...

Macaca mulatta

Synonyms: GNRH, LHRH
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Disease relevance of LHRH


High impact information on LHRH

  • As injected LHRH agonists cause impairment of gonadal function and directly inhibit FSH-induced changes in Leydig cell function through specific membrane receptors, this 'LHRH-like' factor has all the correct credentials for the postulated messenger between the Sertoli and Leydig cells [6].
  • Sertoli-Leydig cell communication via an LHRH-like factor [6].
  • Here, we strengthen this case by demonstrating that seminiferous tubules from both the rat and the stumptailed macaque (Macaca arctoides) contain a factor which has LHRH-like receptor-binding and biological activity in vitro, but which is immunologically distinct from native LHRH [6].
  • In fact, y-aminobutyric acid (GABA) appears to be an inhibitory neurotransmitter responsible for restricting LHRH release before the onset of puberty in female rhesus monkeys [7].
  • Recent studies suggest that during the prepubertal period an inhibitory neuronal system suppresses LHRH release and that during the subsequent maturation of the hypothalamus this prepubertal inhibition is removed, allowing the adult pattern of pulsatile LHRH release [7].

Chemical compound and disease context of LHRH


Biological context of LHRH

  • The present study was undertaken to examine the hypothesis that hypothalamic expression of the TGF alpha gene and its receptor changes in relation to the stage of sexual development in nonhuman primates, and to determine whether these changes are accompanied by corresponding alterations in LHRH gene expression [10].
  • The effects of acute cocaine administration on synthetic LHRH-stimulated anterior pituitary hormones (LH, FSH, and PRL) were studied in 6 female rhesus monkeys during the follicular phase of the menstrual cycle (days 4-7) [11].
  • In a second experiment, infusion of LHRH agonist was started during the luteal phase and extended for 90 days [12].
  • In the second cycle, starting on day 1 after ovulation, the animals received daily administration of a potent inhibitory LHRH analog, [N-Ac-D-Trp1,3,D-p-Cl-Phe1,D-Phe6,D-Ala10]-LH-RH (N = 5) or vehicle (N = 5) until the onset of vaginal bleeding [13].
  • Since sex differences in LHRH response to NPY were not present, data from males and females were combined for analysis [14].

Anatomical context of LHRH

  • In primates the LHRH neurosecretory system is already active during the neonatal period but subsequently enters a dormant state in the juvenile/prepubertal period [7].
  • We examined the effect of treatment with a LH-releasing hormone (LHRH) agonist (Ag), antagonist (Ant), or Ant and androgen (Ant/And) for the first 4 months of postnatal life on lymphocyte subsets and cellular and humorally mediated immune responses in juvenile and adult male monkeys [15].
  • Reactive axons in the median eminence appeared to originate from the positive perikarya in the medial basal hypothalamus; this projection forms a tubero-infundibular tract containing LHRH [16].
  • By the second week a number of LHRH cells (15.7 x 13.6 microns) with neurites started to migrate out from PL explants, whereas some still remained in the PL [17].
  • Moreover, immunocytochemical staining revealed that in all OP monkeys, small, round, and immature LHRH-positive cells with fine short processes were found in the third ventricle and/or median eminence-stalk region, whereas no similar LHRH cells were found in CB-transplanted monkeys [18].

Associations of LHRH with chemical compounds

  • In addition, it appears that the reduction in tonic GABA inhibition allows an increase in the release of glutamate as well as other neurotransmitters, which contributes to the increase in pubertal LHRH release [7].
  • Neither gonadal steroid hormones nor the absence of facilitatory neuronal inputs to LHRH neurons is responsible for the low levels of LHRH release before the onset of puberty in primates [7].
  • GABA, bicuculline (a GABAA receptor blocker), and 2-hydroxysaclofen (a GABAB receptor blocker) were directly infused into the stalk-median eminence while perfusates were collected for LHRH determination [19].
  • Bicuculline, but not saclofen, induced a large and prompt increase in LHRH release in prepubertal monkeys, whereas it stimulated LHRH release slightly in pubertal monkeys [19].
  • The effect of continuous administration of an LHRH agonist for 14 days on follicular estradiol secretion was studied in adult female stumptailed macaque monkeys [12].

Regulatory relationships of LHRH

  • Direct infusion of AS GAD67 (1 microM) into the stalk-median eminence (S-ME) for 5 h stimulated LHRH release in both prepubertal and pubertal monkeys [20].
  • NPY infusion into the S-ME stimulated LHRH release in a dose-dependent manner (P less than 0.001) [14].

Other interactions of LHRH

  • DNA fragments complementary to the coding regions of the rhesus monkey TGF alpha, EGFR and LHRH genes were cloned by reverse transcription-polymerase chain reaction (RT-PCR), sequenced and used to prepare monkey-specific antisense RNA probes [10].
  • Second, effects of antisense oligodeoxynucleotides (D-oligos) for GAD67 and GAD65 mRNAs on LHRH release were examined in conscious female rhesus monkeys at the prepubertal stage using a push-pull perfusion method [21].
  • 2) How does NPY release relate to LHRH release [22]?

Analytical, diagnostic and therapeutic context of LHRH

  • The animals in the control group had no significant changes in LH or T levels, whereas those treated with the lowest dose of LHRH antagonist (10 micrograms) had decreased T levels in the absence of changes in LH [23].
  • Perfusate samples from the stalk-median eminence (S-ME) were obtained through a push-pull cannula at 10-min intervals for 12 h, and the amount of LHRH in samples were determined with RIA [14].
  • In the prepubertal group (n = 4), mean LHRH levels were 0.8 +/- 0.5 pg/ml.10 min during the 90 min before the first electrical stimulation and increased to 6.1 +/- 2.9 pg/ml.10 min during the 90 min after the sixth stimulation [24].
  • These data indicate that castration selectively affects androgen metabolism and LHRH content in discrete regions of the brain of male monkeys and suggest that aromatase and 5 alpha-reductase are regulated differentially in the primate brain [25].
  • In a previous study we found that ovariectomy resulted in an increase in both LHRH release and LH release in pubertal monkeys but not in prepubertal monkeys [26].


  1. Reversal of testicular function after prolonged suppression with an LHRH agonist in rhesus monkeys. Sundaram, K., Keizer-Zucker, A., Thau, R.B., Bardin, C.W. J. Androl. (1987) [Pubmed]
  2. Chemotherapy-induced premature ovarian failure: mechanisms and prevention. Ataya, K., Moghissi, K. Steroids (1989) [Pubmed]
  3. Effects of an LH-releasing hormone antagonist on the secretion of LH, FSH, prolactin and ovarian steroids at different stages of the luteal phase in the stumptailed macaque (Macaca arctoides). Fraser, H.M., Abbott, M., Laird, N.C., McNeilly, A.S., Nestor, J.J., Vickery, B.H. J. Endocrinol. (1986) [Pubmed]
  4. [Ac-D-NAL(2)1,4FD-Phe2,D-Trp3,D-Arg6]-LHRH, a potent antagonist of LHRH, produces transient edema and behavioral changes in rats. Schmidt, F., Sundaram, K., Thau, R.B., Bardin, C.W. Contraception. (1984) [Pubmed]
  5. Active immunization of stumptailed macaque monkeys against luteinizing hormone releasing hormone, and its effects on menstrual cycles, ovarian steroids and positive feedback. Fraser, H.M. J. Reprod. Immunol. (1983) [Pubmed]
  6. Sertoli-Leydig cell communication via an LHRH-like factor. Sharpe, R.M., Fraser, H.M., Cooper, I., Rommerts, F.F. Nature (1981) [Pubmed]
  7. Neurobiological mechanisms of the onset of puberty in primates. Terasawa, E., Fernandez, D.L. Endocr. Rev. (2001) [Pubmed]
  8. Inhibition of folliculogenesis in the monkey following early follicular phase administration of an LRH agonist. Wilks, J.W. Acta Endocrinol. (1984) [Pubmed]
  9. Comparison of the subcutaneous and intranasal administration of an LH-RH antagonist ([N-Ac-D-p-Cl-Phe1,2,D-Trp3,D-Arg6,D-Ala10]-LH-RH) in the rhesus monkey. Asch, R.H., Balmaceda, J.P., Neves de Castro, M., Schally, A.V. Advances in contraception : the official journal of the Society for the Advancement of Contraception. (1985) [Pubmed]
  10. Developmental expression of the genes encoding transforming growth factor alpha and its receptor in the hypothalamus of female rhesus macaques. Ma, Y.J., Costa, M.E., Ojeda, S.R. Neuroendocrinology (1994) [Pubmed]
  11. Cocaine effects on luteinizing hormone-releasing hormone-stimulated anterior pituitary hormones in female rhesus monkey. Mello, N.K., Mendelson, J.H., Drieze, J., Kelly, M. J. Clin. Endocrinol. Metab. (1990) [Pubmed]
  12. Suppression of follicular maturation by infusion of a luteinizing hormone-releasing hormone agonist starting during the late luteal phase in the stumptailed macaque monkey. Fraser, H.M., Sandow, J. J. Clin. Endocrinol. Metab. (1985) [Pubmed]
  13. Suppression of postovulatory gonadotropin levels does not affect corpus luteum function in rhesus monkeys. Balmaceda, J.P., Borghi, M.R., Coy, D.H., Schally, A.V., Asch, R.H. J. Clin. Endocrinol. Metab. (1983) [Pubmed]
  14. Infusion of neuropeptide Y into the stalk-median eminence stimulates in vivo release of luteinizing hormone-release hormone in gonadectomized rhesus monkeys. Woller, M.J., Terasawa, E. Endocrinology (1991) [Pubmed]
  15. Neonatal treatment with luteinizing hormone-releasing hormone analogs alters peripheral lymphocyte subsets and cellular and humorally mediated immune responses in juvenile and adult male monkeys. Mann, D.R., Ansari, A.A., Akinbami, M.A., Wallen, K., Gould, K.G., McClure, H.M. J. Clin. Endocrinol. Metab. (1994) [Pubmed]
  16. The distribution of luteinizing hormone-releasing hormone (LHRH) in the hypothalamus of the rhesus monkey. Light microscopic studies using immunoperoxidase technique. Silverman, A.J., Antunes, J.L., Ferin, M., Zimmerman, E.A. Endocrinology (1977) [Pubmed]
  17. A primary cell culture system of luteinizing hormone releasing hormone neurons derived from embryonic olfactory placode in the rhesus monkey. Terasawa, E., Quanbeck, C.D., Schulz, C.A., Burich, A.J., Luchansky, L.L., Claude, P. Endocrinology (1993) [Pubmed]
  18. Transplantation of the fetal olfactory placode restores reproductive cycles in female rhesus monkeys (Mucaca mulatta) bearing lesions in the medial basal hypothalamus. Saitoh, Y., Luchansky, L.L., Claude, P., Terasawa, E. Endocrinology (1995) [Pubmed]
  19. gamma-Aminobutyric acid is an inhibitory neurotransmitter restricting the release of luteinizing hormone-releasing hormone before the onset of puberty. Mitsushima, D., Hei, D.L., Terasawa, E. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  20. A role of gamma-amino butyric acid (GABA) and glutamate in control of puberty in female rhesus monkeys: effect of an antisense oligodeoxynucleotide for GAD67 messenger ribonucleic acid and MK801 on luteinizing hormone-releasing hormone release. Kasuya, E., Nyberg, C.L., Mogi, K., Terasawa, E. Endocrinology (1999) [Pubmed]
  21. Role of glutamic acid decarboxylase in the prepubertal inhibition of the luteinizing hormone releasing hormone release in female rhesus monkeys. Mitsushima, D., Marzban, F., Luchansky, L.L., Burich, A.J., Keen, K.L., Durning, M., Golos, T.G., Terasawa, E. J. Neurosci. (1996) [Pubmed]
  22. Neuropeptide Y is a neuromodulator of pulsatile luteinizing hormone-releasing hormone release in the gonadectomized rhesus monkey. Woller, M.J., McDonald, J.K., Reboussin, D.M., Terasawa, E. Endocrinology (1992) [Pubmed]
  23. Inhibition of serum luteinizing hormone and testosterone with an inhibitory analog of luteinizing hormone-releasing hormone in adult male rhesus monkeys. Burgos-Briceño, L.A., Schally, A.V., Bartke, A., Asch, R.H. J. Clin. Endocrinol. Metab. (1984) [Pubmed]
  24. Effects of electrical stimulation of the medial basal hypothalamus on the in vivo release of luteinizing hormone-releasing hormone in the prepubertal and peripubertal female monkey. Claypool, L.E., Watanabe, G., Terasawa, E. Endocrinology (1990) [Pubmed]
  25. Regulation of androgen metabolism and luteinizing hormone-releasing hormone content in discrete hypothalamic and limbic areas of male rhesus macaques. Roselli, C.E., Stadelman, H., Horton, L.E., Resko, J.A. Endocrinology (1987) [Pubmed]
  26. Negative feedback effects of estrogen on luteinizing hormone-releasing hormone release occur in pubertal, but not prepubertal, ovariectomized female rhesus monkeys. Chongthammakun, S., Terasawa, E. Endocrinology (1993) [Pubmed]
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