GONADOTROPIN CONTROL OF FOLLICULAR FUNCTION

It has been known for over 50 years that both follicle-stimulating hor mone (FSH) and luteinizing hormone (LH) are required to stimulate both follicular development and oestradiol synthesis. However, previous ex periments employing FSH and LH preparations (whether of pituitary or u rinary origin) have not been able to answer unequivocally, whether an observed response was solely due to either FSH or LH because they were not pure preparations. In view of the recent availability of both 100 % pure recombinant human FSH and recombinant human LH, we now have a u nique opportunity to test their contribution in the regulation of ovar ian function. Such rexperiments may have important clinical implicatio ns as they offer a means to interpret the effect of 'pure' FSH prepara tions when used to stimulate ovarian function in women undergoing diff erent therapeutic regimens. To test the contribution of LH to optimize ovarian responsiveness to FSH, 21-day-old hypophysectomized, immature , female rats were treated for a 2-day period with varying total doses of rec-FSH (30-72 IU and/or rec-LH at 12-hourly intervals. At 48 h af ter the first injection, ovaries were removed, weighed and used to iso late granulosa and thecal interstitial cells for assessment of basal a nd gonadotrophin-responsive steroidogenesis in vitro; homogenized to e xtract total RNA for Northern analysis of 17-hydroxylase/C-17-20-lyase (cytochrome P-450(C17)); mRMA; or examined using in situ hybridizatio n to determine the expression of P-450(C17) in the rat graafian follic le. The experiments demonstrated the potential for rec-FSH to influenc e LH-responsive androgen synthesis (via a paracrine mechanism) which i nvolves an up-regulation of thecal P-450(C17) mRNA. Inhibin is a stron g candidate for mediating granulosa-on-theca paracrine signalling. Ton ic stimulation by LH is required to facilitate thecal responsiveness t o this rec-FSH-activated paracrine signal(s).