Effect of the human follicle-stimulating hormone-binding inhibitor and its N-terminal fragment on follicle-stimulating hormone-induced progesterone secretion by granulosa cells in vitro

J Biosci. 2007 Sep;32(6):1185-94. doi: 10.1007/s12038-007-0120-2.

Abstract

Intrafollicular factors play an important role in folliculogenesis. The follicle-stimulating hormone (FSH)-binding inhibitor (FSHBI), purified by our laboratory from human ovarian follicular fluid, has been shown to suppress ovulation and induce follicular atresia/apoptosis in mice as well as impair fertility in marmosets, the New World monkeys. The octapeptide, a peptide corresponding to the N-terminal region of human FSHBI (hFSHBI), has been synthesized and also shows FSHBI activity in vitro. In the present study, we have attempted to identify the mechanism of action of the peptide in granulosa cell cultures. Rat granulosa cell cultures were treated with varying concentrations of the octapeptide or partially purified hFSHBI (gel chromatography fraction hGF 2) in the presence or absence of human FSH (hFSH) and the amount of progesterone (P;4) secreted in the culture supernatants after 3 h/48 h was estimated. Both hGF2 and the octapeptide failed to alter basal levels as well as 8-bromo cAMP-induced P;4 production, while FSH-induced P 4 secretion was inhibited in a dose-dependent manner. These studies reveal that the octapeptide, a fragment of FSHBI, and the native protein have similar activity in vitro and both compounds alter FSH action at the receptor level upstream of cAMP formation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / physiology*
  • Cells, Cultured
  • Cyclic AMP / metabolism
  • Down-Regulation / physiology*
  • Female
  • Follicle Stimulating Hormone / antagonists & inhibitors
  • Follicle Stimulating Hormone / physiology*
  • Glycopeptides / physiology*
  • Granulosa Cells / metabolism*
  • Humans
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Peptide Fragments / physiology*
  • Progesterone / antagonists & inhibitors
  • Progesterone / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, FSH / antagonists & inhibitors*
  • Receptors, FSH / metabolism

Substances

  • Carrier Proteins
  • FSH-BI protein, human
  • Glycopeptides
  • Intercellular Signaling Peptides and Proteins
  • Peptide Fragments
  • Receptors, FSH
  • intraovarian peptides
  • Progesterone
  • Follicle Stimulating Hormone
  • Cyclic AMP