Insulin-like growth factor-I selectively stimulates cholesterol side-chain cleavage expression in ovarian theca-interstitial cells.
Evidence accumulating in the literature supports the concept that insulin-like growth factor I (IGF-I) may be an important local regulator of ovarian function. Recent studies have demonstrated that IGF-I synergistically augments LH stimulation of theca-interstitial cell (TIC) androgen biosynthesis. The purpose of the present studies was to begin to elucidate the molecular mechanisms of the interaction between IGF-I and LH. TIC were purified from ovaries of hypophysectomized immature rats by Percoll gradient centrifugation. When isolated TIC (5 x 10(6) viable cells per dish) were cultured (4 days) in serum-free medium, low amounts (less than 10 ng/ml) of androsterone were produced. Basal androsterone production was not changed by incubation with IGF-I (30 ng/ml). Treatment with LH (50 ng/ml) caused an 85-fold stimulation of androsterone synthesis that was further increased 2.1-fold by concomitant treatment with IGF-I. Immunoblot analysis demonstrated that untreated TIC contained low levels of 17 alpha-hydroxylase/C17-20 lyase enzyme (P450(17 alpha] that were unchanged by incubation with IGF-I alone. LH treatment increased P450(17 alpha) content 5.5-fold and coincubation with LH plus IGF-I increased P450(17 alpha) content 16-fold above control levels. Cholesterol side chain cleavage enzyme (P450scc) was readily detected in immunoblots from untreated TIC. P450scc content was increased 2.6-fold by LH treatment and 4.2-fold by LH plus IGF-I. Interestingly, IGF-I alone induced a 2-fold increase in P450scc. To determine if the increases in P450scc content were associated with increased enzyme activity, progesterone production was measured.(ABSTRACT TRUNCATED AT 250 WORDS)
Magoffin
D A
DA
Department of Reproductive Medicine, University of California, San Diego, La Jolla 92093.
Kurtz
K M
KM
Erickson
G F
GF
D000728:Androgens / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D007986:Luteinizing Hormone / Q000494:pharmacology; D011374:Progesterone / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013002:Somatomedins / Q000502:physiology*; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D013799:Theca Cells / Q000166:cytology* / Q000201:enzymology
D000728:Androgens; D012333:RNA, Messenger; D013002:Somatomedins; D011374:Progesterone; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme