The role of calmodulin antagonists on steroidogenesis by fetal zone cells of the human fetal adrenal gland

B. R. Carr, W. E. Rainey, J. I. Mason

Research output: Contribution to journalArticle

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Abstract

The adrenal gland of the human fetus (HFA) is relatively large compared to that of the adult and exhibits an extremely high rate of steroidogenesis both in vivo and in vitro. The fetal zone cells make up 80-85% of the volume of the HFA and are the major site of steroid production during fetal development. We have recently demonstrated that calcium is involved in the regulation of steroideogenesis in fetal zone cells of the HFA. There is considerable evidence that many actions of calcium within cells are mediated by the calcium-binding protein calmodulin. The purpose of the present investigation was to determine if calmodulin also plays a role in HFA steroidogenesis. To investigate this possibility, the fetal zone was dissected from fetal adrenals of first and second trimester human abortuses. After collagenase digestion of the tissue, dispersed fetal zone cells were maintained in a Krebs-Ringers medium at 37 C for a 3-h incubation. Cells were incubated with and without ACTH (10-8 M) in the presence of the calmodulin inhibitors trifluoperazine (TFP), chlorpromazine (CPZ), and calmidazolium (CAL) at concentrations of 5-100 μM. The media were assayed for contents of dehydroepiandrosterone sulfate (DS), cortisol (F), pregnenolone, and cAMP by RIA. The addition of ACTH stimulated F secretion 5- to 10-fold compared to that in control fetal zone cells. DS secretion increased up to 5-fold and pregnenolone about 2-fold in the presence of ACTH compared to values in control cells. ACTH also stimulated cAMP secretion by 10-fold compared to that in control cells. The addition of TFP, CPZ, and CAL significantly inhibited ACTH-stimulated DS, F, and pregnenolone secretion in a dose-related fashion to near-control levels. We observed that TFP, CPZ, and CAL inhibited cAMP accumulation as well as Bu2cAMP-stimulated steroid secretion. The metabolism of 22R-hydroxycholesterol to pregnenolone was inhibited by TFP and CPZ, but not by CAL. These studies suggest that calmodulin plays a role in regulating steroidogenesis in fetal zone cells of the HFA.

Original languageEnglish (US)
Pages (from-to)995-999
Number of pages5
JournalEndocrinology
Volume120
Issue number3
StatePublished - 1987

Fingerprint

Calmodulin
Adrenal Glands
calmidazolium
Trifluoperazine
Pregnenolone
Adrenocorticotropic Hormone
Chlorpromazine
Dehydroepiandrosterone Sulfate
Fetus
Steroids
Calcium
Calcium-Binding Proteins
Second Pregnancy Trimester
Collagenases
First Pregnancy Trimester
Fetal Development
Hydrocortisone
Digestion

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

The role of calmodulin antagonists on steroidogenesis by fetal zone cells of the human fetal adrenal gland. / Carr, B. R.; Rainey, W. E.; Mason, J. I.

In: Endocrinology, Vol. 120, No. 3, 1987, p. 995-999.

Research output: Contribution to journalArticle

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