Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. 1990 Jul; 87(13): 5163–5167.

Luteinizing hormone-releasing hormone neurons express Fos protein during the proestrous surge of luteinizing hormone.


The ability of luteinizing hormone-releasing hormone (LHRH) neurons to express the oncogene c-fos was examined during the estrous cycle in rats. The immunocytochemical localization of the c-fos-encoded antigen, Fos, was coupled with the immunocytochemical localization of LHRH. LHRH neurons showed no Fos immunoreactivity during diestrus-1, diestrus-2, estrus, or the morning of proestrus. However, Fos was expressed in LHRH neurons from 1600 to 2200 hours during proestrus. The timing of onset of Fos expression in LHRH neurons during proestrus suggests a strong correlation with increased LH secretion. Pentobarbital, which blocks the preovulatory LH surge, blocked Fos expression in LHRH neurons, but the LHRH neurons expressed Fos on the following afternoon at the time of the expected delayed LH surge. Not all LHRH neurons expressed Fos during the LHRH surge. Approximately half of the LHRH neurons were activated in the preoptic area and anterior hypothalamus; more anteriorly positioned LHRH neurons did not express Fos, resulting in an overall stimulation of 40% of the LHRH neurons. These data provide direct evidence that stimulation of LHRH neurons during proestrus takes place at the LHRH cell bodies, and identify the specific population of LHRH neurons which are activated.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Fraser HM, Baker TG. Changes in the ovaries of rats after immunization against luteinizing hormone releasing hormone. J Endocrinol. 1978 Apr;77(1):85–93. [PubMed]
  • Blake CA, Kelch RP. Administration of antiluteinizing hormone-releasing hormone serum to rats: effects on periovulatory secretion of luteinizing hormone and follicle-stimulating hormone. Endocrinology. 1981 Dec;109(6):2175–2179. [PubMed]
  • Eskay RL, Mical RS, Porter JC. Relationship between luteinizing hormone releasing hormone concentration in hypophysial portal blood and luteinizing hormone release in intact, castrated, and electrochemically-stimulated rats. Endocrinology. 1977 Feb;100(2):263–270. [PubMed]
  • Levine JE, Ramirez VD. Luteinizing hormone-releasing hormone release during the rat estrous cycle and after ovariectomy, as estimated with push-pull cannulae. Endocrinology. 1982 Nov;111(5):1439–1448. [PubMed]
  • Park OK, Ramirez VD. Spontaneous changes in LHRH release during the rat estrous cycle, as measured with repetitive push-pull perfusions of the pituitary gland in the same female rats. Neuroendocrinology. 1989 Jul;50(1):66–72. [PubMed]
  • Rasmussen DD, Kennedy BP, Ziegler MG, Nett TM. Endogenous opioid inhibition and facilitation of gonadotropin-releasing hormone release from the median eminence in vitro: potential role of catecholamines. Endocrinology. 1988 Dec;123(6):2916–2921. [PubMed]
  • Negro-Vilar A, Ojeda SR, McCann SM. Catecholaminergic modulation of luteinizing hormone-releasing hormone release by median eminence terminals in vitro. Endocrinology. 1979 Jun;104(6):1749–1757. [PubMed]
  • Valença MM, Johnston CA, Ching M, Negro-Vilar A. Evidence for a negative ultrashort loop feedback mechanism operating on the luteinizing hormone-releasing hormone neuronal system. Endocrinology. 1987 Dec;121(6):2256–2259. [PubMed]
  • Dragunow M, Robertson HA. Generalized seizures induce c-fos protein(s) in mammalian neurons. Neurosci Lett. 1987 Nov 23;82(2):157–161. [PubMed]
  • Morgan JI, Cohen DR, Hempstead JL, Curran T. Mapping patterns of c-fos expression in the central nervous system after seizure. Science. 1987 Jul 10;237(4811):192–197. [PubMed]
  • Sharp FR, Gonzalez MF, Sharp JW, Sagar SM. c-fos expression and (14C) 2-deoxyglucose uptake in the caudal cerebellum of the rat during motor/sensory cortex stimulation. J Comp Neurol. 1989 Jun 22;284(4):621–636. [PubMed]
  • Sagar SM, Sharp FR, Curran T. Expression of c-fos protein in brain: metabolic mapping at the cellular level. Science. 1988 Jun 3;240(4857):1328–1331. [PubMed]
  • Menétrey D, Gannon A, Levine JD, Basbaum AI. Expression of c-fos protein in interneurons and projection neurons of the rat spinal cord in response to noxious somatic, articular, and visceral stimulation. J Comp Neurol. 1989 Jul 8;285(2):177–195. [PubMed]
  • Hunt SP, Pini A, Evan G. Induction of c-fos-like protein in spinal cord neurons following sensory stimulation. Nature. 1987 Aug 13;328(6131):632–634. [PubMed]
  • Greenberg ME, Greene LA, Ziff EB. Nerve growth factor and epidermal growth factor induce rapid transient changes in proto-oncogene transcription in PC12 cells. J Biol Chem. 1985 Nov 15;260(26):14101–14110. [PubMed]
  • Hoffman GE, Lee WS, Attardi B, Yann V, Fitzsimmons MD. Luteinizing hormone-releasing hormone neurons express c-fos antigen after steroid activation. Endocrinology. 1990 Mar;126(3):1736–1741. [PubMed]
  • Shirley B, Wolinsky J, Schwartz NB. Effects of a single injection of an estrogen antagonist on the estrous cycle of the rat. Endocrinology. 1968 May;82(5):959–968. [PubMed]
  • EVERETT JW, SAWYER CH. A 24-hour periodicity in the "LH-release apparatus" of female rats, disclosed by barbiturate sedation. Endocrinology. 1950 Sep;47(3):198–218. [PubMed]
  • Watson RE, Jr, Wiegand SJ, Clough RW, Hoffman GE. Use of cryoprotectant to maintain long-term peptide immunoreactivity and tissue morphology. Peptides. 1986 Jan-Feb;7(1):155–159. [PubMed]
  • Hoffman GE. Organization of LHRH cells: differential apposition of neurotensin, substance P and catecholamine axons. Peptides. 1985 May-Jun;6(3):439–461. [PubMed]
  • Fox SR, Smith MS. Changes in the pulsatile pattern of luteinizing hormone secretion during the rat estrous cycle. Endocrinology. 1985 Apr;116(4):1485–1492. [PubMed]
  • Bourguignon JP, Gerard A, Mathieu J, Simons J, Franchimont P. Pulsatile release of gonadotropin-releasing hormone from hypothalamic explants is restrained by blockade of N-methyl-D,L-aspartate receptors. Endocrinology. 1989 Aug;125(2):1090–1096. [PubMed]
  • Jennes L, Stumpf WE. Gonadotropin-releasing hormone immunoreactive neurons with access to fenestrated capillaries in mouse brain. Neuroscience. 1986 Jun;18(2):403–416. [PubMed]
  • Silverman AJ, Jhamandas J, Renaud LP. Localization of luteinizing hormone-releasing hormone (LHRH) neurons that project to the median eminence. J Neurosci. 1987 Aug;7(8):2312–2319. [PubMed]
  • Merchenthaler I, Setalo G, Csontos C, Petrusz P, Flerko B, Negro-Vilar A. Combined retrograde tracing and immunocytochemical identification of luteinizing hormone-releasing hormone- and somatostatin-containing neurons projecting to the median eminence of the rat. Endocrinology. 1989 Dec;125(6):2812–2821. [PubMed]
  • Hoffman GE, Gibbs FP. LHRH pathways in rat brain: 'deafferentation' spares a sub-chiasmatic LHRH projection to the median eminence. Neuroscience. 1982;7(8):1979–1993. [PubMed]
  • Bond CT, Hayflick JS, Seeburg PH, Adelman JP. The rat gonadotropin-releasing hormone: SH locus: structure and hypothalamic expression. Mol Endocrinol. 1989 Aug;3(8):1257–1262. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...