Synthesis of the allylic regulatory steroid, 3 alpha-hydroxy-4-pregnen-20-one, by rat granulosa cells and its regulation by gonadotropins.
The production of the allylic regulatory steroid 3 alpha-hydroxy-4-pregnen-20-one (3 alpha HP) in the rat ovary was examined and compared to progesterone levels through use of specific RIAs that had been validated by capillary gas chromatography-mass spectrometry (GC/MS). Results showed that serum levels of 3 alpha HP are comparable to levels of progesterone at all ages examined. In the 4-day cycling rat, serum levels of 3 alpha HP were highest during diestrus and lowest during proestrus and estrus, while serum FSH levels were highest during proestrus/estrus and lowest during diestrus. Hypophysectomy resulted in decreases in ovarian and serum 3 alpha HP. Treatment of hypophysectomized rats with eCG, but not hCG, increased ovarian and serum 3 alpha HP, while serum progesterone was elevated by treatment with hCG. Ovariectomy resulted in a 55-60% reduction in serum 3 alpha HP, indicating that ovaries are a substantial, but not exclusive, source of 3 alpha HP in serum. As further evidence, cultures of preparations consisting primarily of either granulosa cells or granulosa/theca "shells" produced 3 alpha HP in time-dependent amounts comparable to those of progesterone. Granulosa cells in culture showed a significant increase in accumulation of 3 alpha HP (and progesterone) due to treatment with FSH, but not LH. In contrast to the granulosa-only cell cultures, follicle shells consisting of theca and granulosa cells responded to either LH or FSH treatment with marked increases in 3 alpha HP; increases resulting from combined treatment (FSH + LH) were significantly greater than those due to each hormone alone, but the increases were not additives.(ABSTRACT TRUNCATED AT 250 WORDS)
Wiebe
J P
JP
Department of Zoology, University of Western Ontario, London, Canada.
De Gannes
G C
GC
Dallaire
M J
MJ
D004092:20-alpha-Dihydroprogesterone / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000097:blood; D000818:Animals; D002478:Cells, Cultured; D004031:Diestrus / Q000502:physiology; D004971:Estrus / Q000502:physiology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000494:pharmacology*; D008401:Gas Chromatography-Mass Spectrometry; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D007016:Hypophysectomy; D007986:Luteinizing Hormone / Q000494:pharmacology*; D010052:Ovariectomy; D011359:Proestrus / Q000502:physiology; D011374:Progesterone / Q000097:blood / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004092:20-alpha-Dihydroprogesterone; C052610:3-hydroxypregn-4-en-20-one; D011374:Progesterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone