Granulosa cell modulation of luteinizing hormone-dependent androgen production by ovarian theca-interstitial cells: a temporal switch from suppression to augmentation stimulated by follicle-stimulating hormone in vitro.
The production of estradiol-17 beta (E2) by granulosa cells (GC) of the dominant follicle is dependent upon LH-stimulated synthesis of androgens by ovarian theca-interstitial cells (TIC). Recent evidence has pointed toward an intrafollicular paracrine system, regulated by FSH and involving GC, that may modulate the LH-dependent production of androgens by TIC. In the present study, the role of GC and FSH in modulating LH-dependent TIC and androsterone production was examined. In cultures of dispersed whole ovarian cells (containing populations of both GC and TIC) from intact immature rats, LH stimulated a 10-fold increase in androsterone production (maximum androsterone = 21.0 +/- 1.1 ng/ml). By comparison, androsterone production was increased 50-fold in LH-stimulated cultures of dispersed whole ovarian cells from hypophysectomized immature rats (108 +/- 18 ng androsterone/ml). The EC50 for LH (0.02 +/- 0.001 ng/ml) was identical in the two cell preparations. We hypothesized that the lesser androgen production by whole ovarian cell cultures from intact rats was due to suppression by the GC. To investigate the role of GC in modulating TIC androgen production, highly purified TIC from immature hypophysectomized rats were cultured in the presence of GC obtained from intact immature rats. Increasing numbers of GC (2.5-100 x 10(3) GC per well) caused a progressive decrease in LH-dependent androsterone production by TIC. Additionally, LH-dependent androsterone production was suppressed by the conditioned medium from recombinant human FSH (rFSH)-stimulated GC (54% of the value for LH-stimulated TIC controls), indicating the involvement of a GC-secreted paracrine factor or factors.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Obstetrics and Gynecology, Cedars-Sinai Research Institute, Los Angeles, California, USA.
R J
RJ
Zachow
D A
DA
Magoffin
D000728:Androgens / Q000096:biosynthesis*; D000738:Androsterone / Q000096:biosynthesis; D000818:Animals; D002478:Cells, Cultured; D004958:Estradiol / Q000096:biosynthesis; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000502:physiology*; D006801:Humans; D007016:Hypophysectomy; D007986:Luteinizing Hormone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013799:Theca Cells / Q000187:drug effects / Q000378:metabolism*
D000728:Androgens; D011994:Recombinant Proteins; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D000738:Androsterone