Effect of luteinizing hormone on follicle stimulating hormone-activated paracrine signalling in rat ovary.
'Pure' follicle stimulating hormone (FSH) and luteinizing hormone (LH) are expected shortly to become available for pharmaceutical use in the clinical setting. To test the contribution of LH to optimal ovarian responsiveness to FSH, 21-day-old hypophysectomized, immature, female rats received four s.c. injections of recombinant human LH (rhLH; total dose 1-10 IU) and/or rhFSH (total dose 30-72 IU) given 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, or homogenized to extract total RNA for Northern analysis of 17-hydroxylase/C17-20-lyase (cytochrome P-450c17 alpha) mRNA. Serum oestradiol and uterine weight were measured as indices of ovarian oestrogen production; androstenedione was measured to reflect ovarian androgen production. Consistent with the two-cell, two-gonadotrophin model of oestrogen synthesis, increased ovarian oestrogen secretion only occurred if both rhFSH and rhLH were given simultaneously. Treatment with rhFSH alone stimulated ovarian weight gain and granulosa cell aromatase activity without oestrogen secretion, whereas rhLH alone stimulated thecal androgen synthesis and androgen secretion. When the total rhLH dose was fixed at 1 IU, giving rise to an unmeasurably low serum concentration of rhLH, additional treatment with rhFSH (30-72 IU) dose-dependently stimulated serum androgen concentrations as well as oestrogen concentrations. The approximately 2.0 kb-sized P-450c17 alpha mRNA transcript was undetectable in the ovaries of untreated control animals but was abundant in the ovaries of positive controls treated with 15 IU of pregnant mare serum gonadotrophin.(ABSTRACT TRUNCATED AT 250 WORDS)
Smyth
C D
CD
Reproductive Endocrinology Laboratory, University of Edinburgh, UK.
Miró
F
F
Howles
C M
CM
Hillier
S G
SG
D000446:Aldehyde-Lyases / Q000235:genetics; D000735:Androstenedione / Q000096:biosynthesis; D000818:Animals; D001141:Aromatase / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004347:Drug Interactions; D005260:Female; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage*; D006107:Granulosa Cells / Q000187:drug effects / Q000201:enzymology; D006728:Hormones / Q000097:blood; D006801:Humans; D007986:Luteinizing Hormone / Q000008:administration & dosage*; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage; D013254:Steroid 17-alpha-Hydroxylase; D013799:Theca Cells / Q000187:drug effects / Q000378:metabolism; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects
D006728:Hormones; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000735:Androstenedione; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D003577:Cytochrome P-450 Enzyme System; D001141:Aromatase; D013254:Steroid 17-alpha-Hydroxylase; D000446:Aldehyde-Lyases