SPATIOTEMPORAL EXPRESSION PATTERNS OF STEROIDOGENIC ACUTE REGULATORY PROTEIN (STAR) DURING FOLLICULAR DEVELOPMENT IN THE RAT OVARY

The steroidogenic acute regulatory protein (StAR) is a vital mitochond rial protein that is indispensable for the synthesis of steroid hormon es in the steroidogenic cells of the adrenal cortex and the gonads. Re cent studies have shown that StAR enhances the conversion of the subst rate for all steroid hormones, cholesterol, into pregnenolone, probabl y by facilitating cholesterol entry into the inner compartment of the mitochondria where the steroidogenic cytochrome P450scc complex reside s. To study the potential of StAR to affect ovarian steroidogenesis du ring follicular development, we examined the time-dependent expression of StAR protein and messenger RNA in PMSG/human CG (hCG)-treated imma ture rats. Western blot analyses and immunohistochemical and RT-PCR me thodologies have revealed a biphasic expression of StAR in the ovaries responding to hormones. The first peak of StAR expression was generat ed by PMSG administration and lasted for 24 h. Furthermore, it was res tricted to the entire network of the ovarian secondary interstitial ti ssue, as well as to a fewer scattered theca-interna cells. The second burst of StAR expression was observed in response to the LH surge, as simulated by hCG. This time, StAR was expressed in the entire theca-in terna and interstitial tissue, as well as in those granulosa cells tha t were confined to periovulatory follicles. Immunoelectron microscopy studies revealed the over 90% of StAR antigenic sites are localized in the inner compartments of the mitochondrion, suggesting a rapid remov al of StAR precursor from the mitochondrial surface, where it is belie ved to exert its activity. Altogether, our observations portray dynami c acute alterations of StAR expression during the process of follicula r maturation in this animal model. Furthermore, if StAR indeed determi nes steroidogenic capacities in the ovary, our findings imply that, in immature rats undergoing hormonally induced first ovulation: 1) the e arly phases of follicular development are supported by androgen produc tion originating from nonfollicular cells; 2) estrogen production in t he granulosa cells of Graafian follicles is nourished by a submaximal androgenic output in the theca-interstitial compartments of the ovary.