We, and others, have recently reported that the ovary is a site of insulin-like growth factor (IGF) I gene expression. It was the objective of the present studies to assess the relative ovarian abundance of IGF-I transcripts with alternative 5′-untranslated (UT) regions, their cellular localization, and hormonal regulation. To this end, a solution hybrklization/RNase protection assay was employed wherein total rat ovarian RNA was hybridized with a 404-base P-labelled rat IGF-I riboprobe corresponding to the Class A 5′ UT variant. As in liver, three protected bands [322 (Class A), 297 (Class B), and 242 (Class C) bases long] were noted, in keeping with established alternative 5′ UT transcripts. The ovarian (as the hepatic) Class C variant proved the most abundant. The ovarian Class B variant was barely detectable-Cellular localization studies revealed these ovarian IGF-I transcripts to be primarily, if not exclusively, of granulosa but not theca-interstitial cell origin. Treatment of immature (21â€23 days old) hypophysectomized rats with adiethylstilbestrol (DES)-containing subcutaneous silastic implant for a total of 5 days resulted in a 2-fold increase in the (densitometrically quantified) abundance of ovarian IGF-I transcripts, a diametrically-opposed effect (2.6-fold decrease) being noted at the level of the liver. Whereas treatment of hypophysectomized rats with oGH by itself (150 ug, qd, sc x5 days) resulted in a 5-fold increase in hepatic IGF-I gene expression, alimited, albeit distinct inhibitory effect was observed on the steady-state levels of ovarian IGF-I mRNA. In contrast, combined treatment with oGH and DES yielded a 3-fold increase in the abundance of ovarian IGF-I transcripts, there being no net alteration in hepatic IGF-I gene expression. Taken together, these findings reveal ovarian expression of the 3 known 5′-UT IGF-I mRNA variants, document the granulosa cell as the main somatic ovarian cell of IGF-I mRNA generation, and indicate that hepatic and ovarian IGF-I gene expression are differentially regulated in diametrically opposed directions.
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