Selective growth hormone/placental lactogen gene transcription and hormone production in pre- and postmenopausal human ovaries.
In addition to effects of pituitary-derived gonadotropins, human GH modulates and regulates intraovarian reproductive processes in a dose-dependent manner via the endocrine GHRH/GH/insulin-like-growth-factor I (IGF-I) axis. Based on increasing evidence that ovarian regulation involves a complex system of putative para/autocrine factors, we investigated the possibility of gene-selective intraovarian GH/placental lactogen (PL) hormone production, with emphasis on differences between pre- and postmenopause. Analysis of both premenopausal (n = 8) and postmenopausal (n = 10) ovarian-derived messenger ribonucleic acid by reverse transcription-PCR, which amplifies all major gene products of the five-member GH/PL gene cluster GH-N, GH-V, PL-A/B, and PL-L, revealed specific transcripts in all specimens. Their share in gene selective expression by analytical restriction enzyme digestion was determined. The expression pattern of GH/PL messenger ribonucleic acid shows PL-A/B > GH-N, which sets it apart from those of pituitary and placenta. Local production of the respective protein hormones was verified by two time-resolved immunofluorometric assays for human PL-A/B and GH-N; significant amounts of these hormones were detected in cytosolic extracts of premenopausal (n = 6; 555.5 +/- 171 ng PL-A/B and 0.8 +/- 0.6 ng GH-N/g tissue wet wt) and postmenopausal (n = 6; 5.2 +/- 2.7 ng PL-A/B and 0.9 +/- 0.6 ng GH-N/g tissue wet wt) ovaries. No difference was observed between pre- and postmenopausal ovarian GH-N contents, but PL values were 2-3 orders of magnitude lower in postmenopausal tissue (P < 0.001). Serum levels of healthy premenopausal (n = 21) and postmenopausal (n = 16) women were less than 0.02 ng PL/mL. In summary, ovarian-derived GH-N and PL-A/B synthesis correlates well with the established local cascade of GHRH, GHRH receptor, GH receptor, IGF-I, and IGF-I receptor as a putative para/autocrine regulator of ovarian reproductive function.
Schwärzler
P
P
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria.
Untergasser
G
G
Hermann
M
M
Dirnhofer
S
S
Abendstein
B
B
Madersbacher
S
S
Berger
P
P
D000328:Adult; D000368:Aged; D005260:Female; D015200:Fluoroimmunoassay; D019382:Human Growth Hormone / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D005810:Multigene Family; D010053:Ovary / Q000502:physiology*; D010928:Placental Lactogen / Q000235:genetics* / Q000378:metabolism*; D017698:Postmenopause / Q000502:physiology*; D011247:Pregnancy; D017697:Premenopause / Q000502:physiology*; D014158:Transcription, Genetic
D019382:Human Growth Hormone; D010928:Placental Lactogen