Calcium mobilization is a prerequisite for the expression of phorbol ester-stimulated luteinizing hormone secretion from pituitaries of male and acutely ovariectomized rats.
Ionomycin, which mobilizes Ca2+, and phorbol 12-myristate 13-acetate (PMA), which activates protein kinase C (PKC), were used to compare the effects/interactions of Ca2+ and PKC on luteinizing hormone (LH) secretion from pituitaries of intact male and acutely ovariectomized (72 h) rats. Quartered pituitaries from donor animals were perifused at 0.25 ml/min and sequential effluent fractions were collected every 10 min. Continuous administration (4 h) of 1 nmol of gonadotropin-releasing hormone (GnRH) resulted in an increase in LH secretion. Cycloheximide (5 mumol) dissociated the GnRH-stimulated LH responses into protein synthesis-independent and -dependent components. While ionomycin (10 mumol) stimulated LH secretion from pituitaries of both sexes by protein synthesis-independent mechanisms, PMA (1 mumol) and the inactive phorbol ester, 4 alpha-phorbol 12,13-didecanoate (PDD), were ineffective secretagogues. However, PMA (but not PDD) interacted synergistically with ionomycin and GnRH to augment LH secretion by protein synthesis-dependent mechanisms. These results suggest a similarity in the effects/interactions of Ca2+ and PKC in gonadotropes from male and ovariectomized rats. If the effects of PMA can be attributed to PKC activation, then it also appears that Ca2+ mobilization is necessary for the manifestation of PKC as a mediator of LH secretion from these gonadotropes. While PKC activity can be divorced from the protein synthesis-independent component of LH release (this component appears to be mediated by Ca2+ mobilization), the enzyme might be involved in amplifying the response to Ca2+ mobilization through synergistic protein synthesis-dependent mechanisms.
Das
S
S
Department of Physiology, University of Saskatchewan, Saskatoon, Canada.
Fahmy
N W
NW
Bourne
G A
GA
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D010052:Ovariectomy; D010703:Phorbol Esters / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D010703:Phorbol Esters; C008876:phorbol-12,13-didecanoate; D007987:Gonadotropin-Releasing Hormone; D015759:Ionomycin; D007986:Luteinizing Hormone; D003513:Cycloheximide; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium