Characterization of relaxin-stimulated cyclic AMP in cultured rat anterior pituitary cells: influence of dopamine, somatostatin and gender.
Relaxin is a hormone associated with pregnancy that relaxes uterine smooth muscle and softens the connective tissues of the cervix and pelvis. In spite of these well-characterized tissue responses, the second messenger system linked to the relaxin receptor and the range of target tissues are only modestly understood. We found that relaxin enhanced the cyclic AMP levels in anterior pituitary cells from adult female rats. Relaxin induced a maximal 5.7 +/- 0.5-fold (mean +/- S.E.M.) stimulation of cyclic AMP accumulation and had an excitatory concentration for half-maximal effect (EC50) of 0.4 +/- 0.1 nM, while human relaxin A and B chains had no such activity (EC50 greater than 1 microM). Pertussis toxin amplified the efficacy of relaxin by 1.5 +/- 0.1-fold, indicating the intervention of a G coupling protein. The response to relaxin was reversible with washing, and desensitized slowly with continuous exposure to relaxin. In an attempt to define the physiological role for relaxin at the anterior pituitary, we found that two of the major hypophysiotrophic hormones of the brain (dopamine and somatostatin) markedly inhibited the relaxin stimulation of cyclic AMP. There was also a significant correlation of the response magnitude with the gender of the donor rat. Anterior pituitary cells from adult males exhibited a mean twofold maximal stimulation after relaxin, compared with the sixfold increase measured in cells from female rats. We hypothesize a novel physiological function of relaxin, that of signalling the feminine anterior pituitary.
Cronin
M J
MJ
Pharmacological Sciences, Genentech Inc., South San Francisco, California 94080.
Malaska
T
T
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D008297:Male; D037342:Pertussis Toxin; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D012065:Relaxin / Q000494:pharmacology*; D012737:Sex Factors; D013004:Somatostatin / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010566:Virulence Factors, Bordetella; D013004:Somatostatin; D012065:Relaxin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D013755:Tetradecanoylphorbol Acetate; D004298:Dopamine