Synergistic actions of estradiol and the insulin-like growth factor somatomedin-C on swine ovarian (granulosa) cells

Johannes D Veldhuis, R. J. Rodgers, R. W. Furlanetto

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Estradiol amplified synergistically the dose- and time-dependent stimulatory actions of human somatomedin-C on progesterone biosynthesis by cultured swine granulosa cells. This facilitative interaction was not attributable to inhibition of the catabolism of progesterone to 20α-hydroxypregn-4-en-3-one, but rather, reflected time-dependent stimulation of pregnenolone synthesis measured in the presence of exogenous soluble sterol substrate for cholesterol side-chain cleavage. Moreover, treatment with somatomedin-C was accompanied by increased synthesis of two immunoprecipitable cholesterol side-chain cleavage constituents, viz. cytochrome P-450(scc) and adrenodoxin. The synergism between estradiol and somatomedin-C was associated with significantly greater specific binding of somatomedin-C in estrogen-treated than control cultures, with no change in apparent receptor affinity. In vitro synergism occurred at somatomedin-C concentrations estimated by sequence-specific immunoassay to be attainable in ovarian follicular fluid in vivo and was specific in that it was not mimicked by the insulin-like peptide relaxin or by epidermal growth factor or fibroblast growth factor. However, high concentrations of insulin-like growth factor II (multiplication-stimulating activity) and insulin were able to interact with estradiol in a facilitative fashion to enhance progesterone production. In addition, the estrogenic component of the synergism was specific, since it was antagonized by the selective antiestrogen LY156758 and was mimicked sparingly by the nonaromatizable androgen 5α-dihydrotestosterone. We conclude that estradiol and somatomedin-C interact synergistically in a time- and dose-dependent manner to enhance the biosynthesis of pregnenolone and progesterone by swine granulosa cells. Since estradiol and somatomedins are present in significant concentrations in the antral fluids of maturing Graafian follicles, we suggest that coordinated trophic effects of estradiol and insulin-like growth factor(s) may effectively prepare granulosa cells for the high rates of progesterone biosynthesis ultimately required after ovulation.

Original languageEnglish (US)
Pages (from-to)530-538
Number of pages9
JournalEndocrinology
Volume119
Issue number2
StatePublished - 1986
Externally publishedYes

Fingerprint

Granulosa Cells
Somatomedins
Insulin-Like Growth Factor I
Estradiol
Swine
Progesterone
Pregnenolone
Insulin-Like Growth Factor II
Adrenodoxin
Cholesterol
Cholesterol Side-Chain Cleavage Enzyme
Insulin
Relaxin
Follicular Fluid
Estrogen Receptor Modulators
Ovarian Follicle
Fibroblast Growth Factors
Dihydrotestosterone
Sterols
Ovulation

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Synergistic actions of estradiol and the insulin-like growth factor somatomedin-C on swine ovarian (granulosa) cells. / Veldhuis, Johannes D; Rodgers, R. J.; Furlanetto, R. W.

In: Endocrinology, Vol. 119, No. 2, 1986, p. 530-538.

Research output: Contribution to journalArticle

Veldhuis, Johannes D ; Rodgers, R. J. ; Furlanetto, R. W. / Synergistic actions of estradiol and the insulin-like growth factor somatomedin-C on swine ovarian (granulosa) cells. In: Endocrinology. 1986 ; Vol. 119, No. 2. pp. 530-538.
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