Gonadotrophin control of follicular function.
It has been known for over 50 years that both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are required to stimulate both follicular development and oestradiol synthesis. However, previous experiments employing FSH and LH preparations (whether of pituitary or urinary 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 unique opportunity to test their contribution in the regulation of ovarian function. Such experiments may have important clinical implications as they offer a means to interpret the effect of 'pure' FSH preparations when used to stimulate ovarian function in women undergoing different 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 after the first injection, ovaries were removed, weighed and used to isolate granulosa and thecal interstitial cells for assessment of basal and gonadotrophin-responsive steroidogenesis in vitro; homogenized to extract total RNA for Northern analysis of 17-hydroxylase/C17-20-lyase (cytochrome P-450C17); mRMA; or examined using in situ hybridization to determine the expression of P-450C17 in the rat graafian follicle. The experiments demonstrated the potential for rec-FSH to influence LH-responsive androgen synthesis (via a paracrine mechanism) which involves an up-regulation of thecal P-450C17 mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Hillier
S G
SG
Reproductive Endocrinology Laboratory, University of Edinburgh Centre for Reproductive Biology, UK.
Smyth
C D
CD
Whitelaw
P F
PF
Miró
F
F
Howles
C M
CM
D000446:Aldehyde-Lyases / Q000235:genetics / Q000378:metabolism; D000728:Androgens / Q000096:biosynthesis; D000818:Animals; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006062:Gonadotropins / Q000502:physiology*; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism; D007016:Hypophysectomy; D007986:Luteinizing Hormone / Q000494:pharmacology; D006080:Ovarian Follicle / Q000502:physiology*; D010053:Ovary / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins; D013254:Steroid 17-alpha-Hydroxylase; D013799:Theca Cells / Q000187:drug effects / Q000378:metabolism
D000728:Androgens; D006062:Gonadotropins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D003577:Cytochrome P-450 Enzyme System; D013254:Steroid 17-alpha-Hydroxylase; D000446:Aldehyde-Lyases