Regulation of luteal cell big stanniocalcin production and secretion.
In mammals, the ovaries have the highest levels of stanniocalcin (STC) gene expression, most or all of which is confined to androgen-producing thecal-interstitial cells (TICs). Ovarian TICs also synthesize a different STC that consists of three high molecular weight species collectively known as big STC. Upon release in response to LH stimulation, TIC-derived big STC is sequestered locally by target cells, particularly steroidogenic cells of the corpus luteum, via a receptor-mediated process. Although there is little or no STC gene expression in luteal cells in the in vivo setting, this report describes how the gene is turned on, STC mRNA becomes readily detectable, and big STC is secreted when bovine luteal cells are cultured in vitro. STC gene expression and secretion were both positively regulated by activation of the adenylate cyclase/protein kinase A signaling pathway (forskolin and 8-bromo-cAMP). However, prostaglandin E2 was the only natural luteal cell ligand capable of replicating the effects of forskolin and 8-bromo-cAMP (LH had no consistent effect). Sex steroids such as 17beta-estradiol, androstenedione, and progesterone significantly decreased luteal cell STC expression and secretion. However, only androstenedione was capable of reducing STC production and secretion to undetectable levels. This report is the first to show that once removed from their normal context within the ovary, luteal cells are capable of synthesizing and secreting big STC. It is also the first to delineate the regulatory mechanisms involved in STC production and secretion by luteal cells. These results therefore suggest that under certain physiological conditions, the corpus luteum could very well serve as a source of STC production.
Paciga
Mark
M
Department of Physiology and Pharmacology, Faculty of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada N6A 5C1.
DiMattia
Gabriel E
GE
Wagner
Graham F
GF
D000728:Androgens / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003338:Corpus Luteum / Q000166:cytology* / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000494:pharmacology; D010120:Oxytocics / Q000494:pharmacology
D000728:Androgens; D005938:Glucocorticoids; D006023:Glycoproteins; D010120:Oxytocics; D004958:Estradiol; C051795:teleocalcin; D003907:Dexamethasone; D007986:Luteinizing Hormone; D015232:Dinoprostone