In vivo regulation of granulosa cell somatomedin-C/insulin-like growth factor I receptors.
The characteristics and regulation of the murine granulosa cell type I insulin-like growth factor (IGF) receptor under in vivo conditions were studied. In vivo treatment of immature hypophysectomized diethylstilbestrol-treated rats with increasing doses (0.3-30 microgram/rat, twice daily) of FSH for 72 h resulted in dose-dependent increments in specific granulosa cell somatomedin-C (Sm-C)/IGF-I binding, peaking (5150 +/- 350 cpm/3 x 10(5) cells) at the 10 micrograms/rat (twice daily) dose level to yield a 2.6-fold increase relative to that in untreated controls. This FSH (10 micrograms/rat, twice daily) effect proved time dependent; the first significant (P less than 0.05) increase in binding (3670 +/- 150 cpm/3 x 10(5) cells) was noted after 48 h of treatment (1.6-fold increase). Significantly, little or no variation was observed for basal Sm-C/IGF-I binding over the course of the experiment, suggesting that this component of Sm-C/IGF-I receptor complement may be independent of the trophic influence(s) of the pituitary gland. Equilibrium competition studies carried out with granulosa cells derived from both control and FSH-treated rats revealed linear Scatchard plots consistent with a single class of noninteracting binding sites, a 2.8-fold increase in FSH-associated Sm-C/IGF-I-binding capacity, but not affinity (Kd control, 1.9 +/- 0.3 nM; kd FSH, 2.6 +/- 0.9 nM). Limited specificity studies of the FSH-induced receptor revealed related peptides to compete for Sm-C/IGF-I binding with a relative rank order of potency of Sm-C/IGF-I much greater than multiplication-stimulating activity greater than insulin, a pattern compatible with a type I IGF receptor. A series of other polypeptides, including porcine relaxin, porcine proinsulin, epidermal growth factor, basic fibroblast growth factor as well as transforming growth factor-alpha and -beta (TGF beta) were nonreactive. Significantly, the induced type I IGF receptor proved functionally coupled to granulosa cell proteoglycan biosynthesis. The ability of FSH (10 micrograms/rat, twice daily) to enhance granulosa cell Sm-C/IGF-I binding was significantly (P less than 0.05) up-regulated (1.53-fold amplification) by ovine GH (100 micrograms/rat, twice daily); a down-regulatory effect (64% inhibition) was observed for a potent GnRH agonist [( D-Ala6,Des-Gly10]GnRH ethyl amide; 25 micrograms/rat, twice daily). Once induced, the Sm-C/IGF-I receptor of the granulosa cell required the continued presence of either FSH or LH for its maintenance; the lactogenic receptor agonist PRL had no effect.(ABSTRACT TRUNCATED AT 400 WORDS)
Adashi
E Y
EY
Department of Obstetrics/Gynecology, University of Maryland School of Medicine, Baltimore 21201.
Resnick
C E
CE
Hernandez
E R
ER
Svoboda
M E
ME
Van Wyk
J J
JJ
D000818:Animals; D004054:Diethylstilbestrol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D006107:Granulosa Cells / Q000378:metabolism*; D013006:Growth Hormone / Q000494:pharmacology; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D011509:Proteoglycans / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism*; D017451:Receptors, Somatomedin; D013997:Time Factors
D011509:Proteoglycans; D017451:Receptors, Somatomedin; D007987:Gonadotropin-Releasing Hormone; D007334:Insulin-Like Growth Factor I; D004054:Diethylstilbestrol; D005640:Follicle Stimulating Hormone; D013006:Growth Hormone; D011972:Receptor, Insulin