Calcium ions modulate hormonally stimulated progesterone production in isolated ovarian cells

Swine granulosa-luteal cells incubated in Ca²⁺-deficient medium (5μM final Ca²⁺ concentration) for short time periods produced diminished quantities of progesterone in response to lutropin. Maximally stimulating effects of prostaglandin E₂ and L-adrenaline were also impaired significantly. Diminished progesterone production could not be attributed to alterations in protein synthesis or cell viability. Under Ca²⁺-deprived conditions, the stimulatory action of cholera toxin, 3-isobutyl-1-methylxanthine and 8-bromo-cyclic AMP were also significantly impeded. Administration of a presumptive antagonist of transmembrane Ca²⁺ influx (verapamil) or of EGTA to chelate extracellular Ca²⁺, significantly decreased the total cellular content of Ca²⁺, and antagonized the actions of lutropin. Micromolar concentrations of trifluoperazine mimicked the suppressive effects of Ca²⁺ deprivation. Conversely, the bivalent-cation ionophore, ionophore A23187, significantly augmented the stimulation of progesterone production by lutropin. Thus the present observations implicate Ca²⁺ in the modulation of hormonally stimulated progesterone production in isolated ovarian cells, and suggest that Ca²⁺ may influence one or more processes distal to, or independent of, cyclic AMP generation. In addition, the susceptibility of progesterone biosynthesis to inhibition by trifluoperazine suggests a possible role for calmodulin in the ovary.