Regulation of corticotropin responsiveness in human fetal adrenal cells

William E. Rainey, Jan M. McAllister, E. William Byrd, J. Ian Mason, Bruce R. Carr

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The human fetal adrenal gland exhibits a high rate of steroidogenesis during fetal development and produces the majority of steroids used by the placenta for estrogen synthesis. Corticotropin appears to be the principal hormonal regulator of steroidogenesis in the fetal adrenal gland. However, little is known concerning the regulation of corticotropin receptors. In this study we examined the long-term regulation of corticotropin responsiveness as measured by the ability of human fetal adrenal gland cells to produce cyclic adenosine monophosphate after corticotropin treatment for 3 hours. We also examined the regulation of corticotropin receptors as determined by iodine 125-labeled corticotropin binding to fetal adrenal cells. Fetal adrenal glands were obtained from second-trimester abortuses. The two distinct zones of the fetal adrenal gland, the definitive zone and the fetal zone, were separated and the tissue mechanically dispersed. Freshly isolated cells responded to corticotropin with a sevenfold to tenfold increase in the production of cyclic adenosine monophosphate, indicating a functional corticotropin receptor-adenylate cyclase coupling. However, when either fetal zone or definitive zone cells were grown and passed in monolayer culture, corticotropin stimulation of cyclic adenosine monophosphate production dropped to only twofold. The loss of corticotropin stimulation of cyclic adenosine monophosphate production occurred with a loss of the steroid-metabolizing enzyme 17α-hydroxylase (P-45017α). Because P-45017α expression can be stimulated after treatment of fetal adrenal gland cells with corticotropin or forskolin, we attempted to increase the ability of corticotropin to stimulate cyclic adenosine monophosphate production in a similar manner. After cells were pretreated with corticotropin (0.1 to 100 nmol/L) or forskolin (0.1 to 100 μmol/L) for 4 days, their ability to produce cyclic adenosine monophosphate in response to corticotropin was examined. Pretreatment with both corticotropin and forskolin caused a dose-dependent increase in the ability of corticotropin to stimulate the production of cyclic adenosine monophosphate. Cells stimulated with corticotropin after pretreatment with forskolin exhibited a 35- to 50-fold increase in cyclic acenosine monophosphate production compared with nontreated cells ({reversed tilde equals}twofold). Corticotropin pretreatment increased responsiveness to a lesser extent than forskolin pretreatment. The increase in corticotropin responsiveness occurred along with an induction of P-45017α enzyme levels. The effect of pretreatment with corticotropin and forskolin on the binding of iodine 125-labeled corticotropin to definitive zone cells was also investigated. Corticotropin pretreatment increased corticotropin receptor binding 2.8 times; forskolin pretreatment increased corticotropin binding by seven times. These data indicate that corticotropin responsiveness and corticotropin receptors in human fetal adrenal cells are regulated by a cyclic adenosine monophosphate-dependent mechanism. This observation is similar to fincings in bovine and ovine adrenal cells where the number of corticotropin receptors is increased by corticotropin or cyclic adenosine monophosphate treatment.

Original languageEnglish (US)
Pages (from-to)1649-1654
Number of pages6
JournalAmerican Journal of Obstetrics and Gynecology
Volume165
Issue number6 PART 1
DOIs
StatePublished - 1991

Fingerprint

Adrenocorticotropic Hormone
Corticotropin Receptors
Cyclic AMP
Colforsin
Adrenal Glands
Iodine
Steroids
Second Pregnancy Trimester
Enzymes

Keywords

  • cell culture
  • corticotropin responsiveness
  • definitive zone cells
  • Fetal adrenal gland
  • fetal zone cells

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynecology

Cite this

Regulation of corticotropin responsiveness in human fetal adrenal cells. / Rainey, William E.; McAllister, Jan M.; Byrd, E. William; Mason, J. Ian; Carr, Bruce R.

In: American Journal of Obstetrics and Gynecology, Vol. 165, No. 6 PART 1, 1991, p. 1649-1654.

Research output: Contribution to journalArticle

Rainey, William E. ; McAllister, Jan M. ; Byrd, E. William ; Mason, J. Ian ; Carr, Bruce R. / Regulation of corticotropin responsiveness in human fetal adrenal cells. In: American Journal of Obstetrics and Gynecology. 1991 ; Vol. 165, No. 6 PART 1. pp. 1649-1654.
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