Lamprey GnRH-III acts on its putative receptor via nitric oxide to release follicle-stimulating hormone specifically

W. H. Yu, S. Karanth, C. A. Mastronardi, S. Sealfon, C. Dean, W. L. Dees, S. M. McCann

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19 Scopus citations


Lamprey gonadotropin-releasing hormone-III (I-GnRH-III), the putative follicle-stimulating hormone (FSH)-releasing factor (FSHRF), exerts a preferential FSH-releasing activity in rats both in vitro and in vivo. To test the hypothesis that I-GnRH-III acts on its own receptors to stimulate gonadotropin release, the functional activity of this peptide at mammalian (m) leutinizing hormone (LH)RH receptors transfected to COS cells was tested. I-GnRH-III activated m-LHRH receptors only at a minimal effective concentration (MEC) of 10-6 M, whereas m-LHRH was active at a MEC of 10-9 M, at least 1,000 times less than that required for I-GnRH-III. In 4-day monolayer cultured cells, I-GnRH-III was similarly extremely weak in releasing either LH or FSH, and, in fact, it released LH at a lower concentration (10-7 M) than that required for FSH release (10-6 M). In this assay, m-LHRH released both FSH and LH significantly at the lowest concentration tested (10-10 M). On the other hand, I-GnRH-III had a high potency to selectively release FSH and not LH from hemipituitaries of male rats. The results suggest that the cultured cells were devoid of FSHRF receptors, thereby resulting in a pattern of FSH and LH release caused by the LHRH receptor. On the other hand, the putative FSH-releasing factor receptor accounts for the selective FSH release by I-GnRH-III when tested on hemipituitaries. Removal of calcium from the medium plus the addition of EGTA, a calcium chelator, suppressed the release of gonadotropins induced by either I-GnRH-III or LHRH, indicating that calcium is required for the action of either peptide. Previous results showed that sodium nitroprusside, a releaser of nitric oxide (NO), causes the release of both FSH and LH from hemipituitaries incubated in vitro. In the present experiments, a competitive inhibitor of NO synthase, L-NG-monomethyl-Larginine (300 μM) blocked the action of I-GnRH-III or partially purified FSHRF. The results indicate that I-GnRH-III and FSHRF act on putative FSHRF receptors by a calcium-dependent NO pathway.

Original languageEnglish
Pages (from-to)786-793
Number of pages8
JournalExperimental Biology and Medicine
Issue number9
StatePublished - Oct 2002


  • FSHRF receptors
  • NO synthase
  • cGMP
  • m-LHRH receptors


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