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. 1994 Feb 15;91(4):1423–1427. doi: 10.1073/pnas.91.4.1423

A second gene for gonadotropin-releasing hormone: cDNA and expression pattern in the brain.

S A White 1, C T Bond 1, R C Francis 1, T L Kasten 1, R D Fernald 1, J P Adelman 1
PMCID: PMC43171  PMID: 8108425

Abstract

In vertebrates, the gonadotropin-releasing hormone (GnRH) decapeptide is secreted from hypothalamic nerve terminals to regulate reproduction via control of synthesis and release of pituitary gonadotropins. Only one GnRH peptide has been found in mammals, with one exception, although numerous other vertebrate species express more than one of the eight known decapeptide forms as shown by immunocytochemical labeling of distinct cell groups in the brain. However, neither the functional nor the evolutionary relationships among these GnRH forms are clear, because only one preprohormone gene sequence from any species has been reported. The most ubiquitous alternative form of GnRH is [His5,Trp7,Tyr8]GnRH (also referred to as chicken-II), which differs from the mammalian sequence at amino acids 5, 7, and 8. This peptide has been shown to have the most potent releasing-hormone activity, although immunocytochemical staining has suggested it is synthesized only in the mesencephalon. Here we report the cloning and expression pattern of the gene for the precursor of this form from the teleost fish Haplochromis burtoni. This is the second GnRH-encoding gene to be characterized in this species. The newly discovered preprohormone gene differs from that previously reported in two ways. First, whereas the original gene predicts only a single associated peptide, this one predicts two associated peptides, both of which appear to be unique. Second, the gene for [His5,Trp7,Tyr8]GnRH is expressed in only one cell group in the mesencephalon. In contrast, the previously reported gene is expressed only in the terminal nerve. The striking differences between the preprohormone structure and localization suggest that the genes coding for the two known GnRH forms in H. burtoni did not arise from a recent duplication event. Interestingly, neither of the two genes found to date in this species is expressed in cells which project from the hypothalamus to the pituitary, suggesting that yet a third gene coding for GnRH may exist.

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Selected References

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  1. Adelman J. P., Mason A. J., Hayflick J. S., Seeburg P. H. Isolation of the gene and hypothalamic cDNA for the common precursor of gonadotropin-releasing hormone and prolactin release-inhibiting factor in human and rat. Proc Natl Acad Sci U S A. 1986 Jan;83(1):179–183. doi: 10.1073/pnas.83.1.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Amano M., Oka Y., Aida K., Okumoto N., Kawashima S., Hasegawa Y. Immunocytochemical demonstration of salmon GnRH and chicken GnRH-II in the brain of masu salmon, Oncorhynchus masou. J Comp Neurol. 1991 Dec 15;314(3):587–597. doi: 10.1002/cne.903140313. [DOI] [PubMed] [Google Scholar]
  3. Amoss M., Burgus R., Blackwell R., Vale W., Fellows R., Guillemin R. Purification, amino acid composition and N-terminus of the hypothalamic luteinizing hormone releasing factor (LRF) of ovine origin. Biochem Biophys Res Commun. 1971 Jul 2;44(1):205–210. doi: 10.1016/s0006-291x(71)80179-1. [DOI] [PubMed] [Google Scholar]
  4. Bennis M., Dubourg P., Gamrani H., Calas A., Kah O. Existence of a GnRH immunoreactive nucleus in the dorsal midbrain tegmentum of the chameleon. Gen Comp Endocrinol. 1989 Aug;75(2):195–203. doi: 10.1016/0016-6480(89)90071-3. [DOI] [PubMed] [Google Scholar]
  5. Bond C. T., Francis R. C., Fernald R. D., Adelman J. P. Characterization of complementary DNA encoding the precursor for gonadotropin-releasing hormone and its associated peptide from a teleost fish. Mol Endocrinol. 1991 Jul;5(7):931–937. doi: 10.1210/mend-5-7-931. [DOI] [PubMed] [Google Scholar]
  6. Chang J. P., Cook H., Freedman G. L., Wiggs A. J., Somoza G. M., de Leeuw R., Peter R. E. Use of a pituitary cell dispersion method and primary culture system for the studies of gonadotropin-releasing hormone action in the goldfish, Carassius auratus. I. Initial morphological, static, and cell column perifusion studies. Gen Comp Endocrinol. 1990 Feb;77(2):256–273. doi: 10.1016/0016-6480(90)90310-i. [DOI] [PubMed] [Google Scholar]
  7. Chou H. F., Johnson A. L., Williams J. B. Luteinizing hormone releasing activity of [Gln8]-LHRH and [His5, Trp7, Tyr8]-LHRH in the cockerel, in vivo and in vitro. Life Sci. 1985 Dec 30;37(26):2459–2465. doi: 10.1016/0024-3205(85)90602-2. [DOI] [PubMed] [Google Scholar]
  8. Conlon J. M., Collin F., Chiang Y. C., Sower S. A., Vaudry H. Two molecular forms of gonadotropin-releasing hormone from the brain of the frog, Rana ribibunda: purification, characterization, and distribution. Endocrinology. 1993 May;132(5):2117–2123. doi: 10.1210/endo.132.5.8477660. [DOI] [PubMed] [Google Scholar]
  9. Davis M. R., Fernald R. D. Social control of neuronal soma size. J Neurobiol. 1990 Dec;21(8):1180–1188. doi: 10.1002/neu.480210804. [DOI] [PubMed] [Google Scholar]
  10. Dellovade T. L., King J. A., Millar R. P., Rissman E. F. Presence and differential distribution of distinct forms of immunoreactive gonadotropin-releasing hormone in the musk shrew brain. Neuroendocrinology. 1993 Aug;58(2):166–177. doi: 10.1159/000126529. [DOI] [PubMed] [Google Scholar]
  11. Douglass J., Civelli O., Herbert E. Polyprotein gene expression: generation of diversity of neuroendocrine peptides. Annu Rev Biochem. 1984;53:665–715. doi: 10.1146/annurev.bi.53.070184.003313. [DOI] [PubMed] [Google Scholar]
  12. Francis R. C., Soma K., Fernald R. D. Social regulation of the brain-pituitary-gonadal axis. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7794–7798. doi: 10.1073/pnas.90.16.7794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Habibi H. R., Peter R. E., Nahorniak C. S., Milton R. C., Millar R. P. Activity of vertebrate gonadotropin-releasing hormones and analogs with variant amino acid residues in positions 5, 7 and 8 in the goldfish pituitary. Regul Pept. 1992 Feb 18;37(3):271–284. doi: 10.1016/0167-0115(92)90620-a. [DOI] [PubMed] [Google Scholar]
  14. Katz I. A., Millar R. P., King J. A. Differential regional distribution and release of two forms of gonadotropin-releasing hormone in the chicken brain. Peptides. 1990 May-Jun;11(3):443–450. doi: 10.1016/0196-9781(90)90040-c. [DOI] [PubMed] [Google Scholar]
  15. King J. A., Millar R. P. Structure of chicken hypothalamic luteinizing hormone-releasing hormone. I. Structural determination on partially purified material. J Biol Chem. 1982 Sep 25;257(18):10722–10728. [PubMed] [Google Scholar]
  16. King J. A., Millar R. P. Structure of chicken hypothalamic luteinizing hormone-releasing hormone. II. Isolation and characterization. J Biol Chem. 1982 Sep 25;257(18):10729–10732. [PubMed] [Google Scholar]
  17. Klungland H., Lorens J. B., Andersen O., Kisen G. O., Alestrøm P. The Atlantic salmon prepro-gonadotropin releasing hormone gene and mRNA. Mol Cell Endocrinol. 1992 Apr;84(3):167–174. doi: 10.1016/0303-7207(92)90027-4. [DOI] [PubMed] [Google Scholar]
  18. Loumaye E., Thorner J., Catt K. J. Yeast mating pheromone activates mammalian gonadotrophs: evolutionary conservation of a reproductive hormone? Science. 1982 Dec 24;218(4579):1323–1325. doi: 10.1126/science.6293058. [DOI] [PubMed] [Google Scholar]
  19. Lovejoy D. A., Fischer W. H., Ngamvongchon S., Craig A. G., Nahorniak C. S., Peter R. E., Rivier J. E., Sherwood N. M. Distinct sequence of gonadotropin-releasing hormone (GnRH) in dogfish brain provides insight into GnRH evolution. Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6373–6377. doi: 10.1073/pnas.89.14.6373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mason A. J., Hayflick J. S., Zoeller R. T., Young W. S., 3rd, Phillips H. S., Nikolics K., Seeburg P. H. A deletion truncating the gonadotropin-releasing hormone gene is responsible for hypogonadism in the hpg mouse. Science. 1986 Dec 12;234(4782):1366–1371. doi: 10.1126/science.3024317. [DOI] [PubMed] [Google Scholar]
  21. Matsuo H., Baba Y., Nair R. M., Arimura A., Schally A. V. Structure of the porcine LH- and FSH-releasing hormone. I. The proposed amino acid sequence. Biochem Biophys Res Commun. 1971 Jun 18;43(6):1334–1339. doi: 10.1016/s0006-291x(71)80019-0. [DOI] [PubMed] [Google Scholar]
  22. Mikami S., Yamada S., Hasegawa Y., Miyamoto K. Localization of avian LHRH-immunoreactive neurons in the hypothalamus of the domestic fowl, Gallus domesticus, and the Japanese quail, Coturnix coturnix. Cell Tissue Res. 1988 Jan;251(1):51–58. doi: 10.1007/BF00215446. [DOI] [PubMed] [Google Scholar]
  23. Millar R. P., Milton R. C., Follett B. K., King J. A. Receptor binding and gonadotropin-releasing activity of a novel chicken gonadotropin-releasing hormone ([His5, Trp7, Tyr8]GnRH) and a D-Arg6 analog. Endocrinology. 1986 Jul;119(1):224–231. doi: 10.1210/endo-119-1-224. [DOI] [PubMed] [Google Scholar]
  24. Miller K. E., Kriebel R. M. Peptidergic innervation of caudal neurosecretory neurons. Gen Comp Endocrinol. 1986 Dec;64(3):396–400. doi: 10.1016/0016-6480(86)90074-2. [DOI] [PubMed] [Google Scholar]
  25. Miyamoto K., Hasegawa Y., Igarashi M., Chino N., Sakakibara S., Kangawa K., Matsuo H. Evidence that chicken hypothalamic luteinizing hormone-releasing hormone is [Gln8]-LH-RH. Life Sci. 1983 Mar 21;32(12):1341–1347. doi: 10.1016/0024-3205(83)90808-1. [DOI] [PubMed] [Google Scholar]
  26. Miyamoto K., Hasegawa Y., Minegishi T., Nomura M., Takahashi Y., Igarashi M., Kangawa K., Matsuo H. Isolation and characterization of chicken hypothalamic luteinizing hormone-releasing hormone. Biochem Biophys Res Commun. 1982 Aug;107(3):820–827. doi: 10.1016/0006-291x(82)90596-4. [DOI] [PubMed] [Google Scholar]
  27. Miyamoto K., Hasegawa Y., Nomura M., Igarashi M., Kangawa K., Matsuo H. Identification of the second gonadotropin-releasing hormone in chicken hypothalamus: evidence that gonadotropin secretion is probably controlled by two distinct gonadotropin-releasing hormones in avian species. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3874–3878. doi: 10.1073/pnas.81.12.3874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ngamvongchon S., Rivier J. E., Sherwood N. M. Structure-function studies of five natural, including catfish and dogfish, gonadotropin-releasing hormones and eight analogs on reproduction in Thai catfish (Clarias macrocephalus). Regul Pept. 1992 Nov 20;42(1-2):63–73. doi: 10.1016/0167-0115(92)90024-o. [DOI] [PubMed] [Google Scholar]
  29. Okuzawa K., Amano M., Kobayashi M., Aida K., Hanyu I., Hasegawa Y., Miyamoto K. Differences in salmon GnRH and chicken GnRH-II contents in discrete brain areas of male and female rainbow trout according to age and stage of maturity. Gen Comp Endocrinol. 1990 Oct;80(1):116–126. doi: 10.1016/0016-6480(90)90155-f. [DOI] [PubMed] [Google Scholar]
  30. Seeburg P. H., Adelman J. P. Characterization of cDNA for precursor of human luteinizing hormone releasing hormone. Nature. 1984 Oct 18;311(5987):666–668. doi: 10.1038/311666a0. [DOI] [PubMed] [Google Scholar]
  31. Sharp P. J., Talbot R. T., Main G. M., Dunn I. C., Fraser H. M., Huskisson N. S. Physiological roles of chicken LHRH-I and -II in the control of gonadotrophin release in the domestic chicken. J Endocrinol. 1990 Feb;124(2):291–299. doi: 10.1677/joe.0.1240291. [DOI] [PubMed] [Google Scholar]
  32. Sherwood N. M., Lovejoy D. A., Coe I. R. Origin of mammalian gonadotropin-releasing hormones. Endocr Rev. 1993 Apr;14(2):241–254. doi: 10.1210/edrv-14-2-241. [DOI] [PubMed] [Google Scholar]
  33. Sherwood N. M., Sower S. A., Marshak D. R., Fraser B. A., Brownstein M. J. Primary structure of gonadotropin-releasing hormone from lamprey brain. J Biol Chem. 1986 Apr 15;261(11):4812–4819. [PubMed] [Google Scholar]
  34. Sherwood N., Eiden L., Brownstein M., Spiess J., Rivier J., Vale W. Characterization of a teleost gonadotropin-releasing hormone. Proc Natl Acad Sci U S A. 1983 May;80(9):2794–2798. doi: 10.1073/pnas.80.9.2794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Sower S. A., Chiang Y. C., Lovas S., Conlon J. M. Primary structure and biological activity of a third gonadotropin-releasing hormone from lamprey brain. Endocrinology. 1993 Mar;132(3):1125–1131. doi: 10.1210/endo.132.3.8440174. [DOI] [PubMed] [Google Scholar]
  36. Suzuki M., Hyodo S., Kobayashi M., Aida K., Urano A. Characterization and localization of mRNA encoding the salmon-type gonadotrophin-releasing hormone precursor of the masu salmon. J Mol Endocrinol. 1992 Aug;9(1):73–82. doi: 10.1677/jme.0.0090073. [DOI] [PubMed] [Google Scholar]
  37. Tsai P. S., Licht P. Differential distribution of chicken-I and chicken-II GnRH in the turtle brain. Peptides. 1993 Mar-Apr;14(2):221–226. doi: 10.1016/0196-9781(93)90033-d. [DOI] [PubMed] [Google Scholar]
  38. White S. A., Fernald R. D. Gonadotropin-releasing hormone-containing neurons change size with reproductive state in female Haplochromis burtoni. J Neurosci. 1993 Feb;13(2):434–441. doi: 10.1523/JNEUROSCI.13-02-00434.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Wright D. E., Demski L. S. Gonadotropin hormone-releasing hormone (GnRH) immunoreactivity in the mesencephalon of sharks and rays. J Comp Neurol. 1991 May 1;307(1):49–56. doi: 10.1002/cne.903070105. [DOI] [PubMed] [Google Scholar]

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