A sex difference in the effect of prostaglandins on hormone-stimulated glycogenolysis in primary cultures of rat hepatocytes

Abstract

E series prostaglandins and their biologically active analogue, 16,16-dimethylprostaglandin E 2 (dimethylprostaglandin E 2), have inhibited hormone-stimulated glycogenolysis in hepatocytes cultured from male rats (Okumura, T., Sago, T. and Saito, K. (1988) Biochim. Biophys. Acta 958, 179–187). However, in the case of female rat hepatocytes, it is evident that dimethylprostaglandin E 2 did not inhibit the glycogenolysis stimulated by glucagon, isoproterenol (β-adrenergic response) or epinephrine (with propranolol, α 1-adrenergic response) in cultures on day 1. Dimethylprostaglandin E 2 inhibited such hormone-stimulated glycogenolysis in cultures on days 2 and 3, but to a lesser extent than in the male-derived cells. The concentration for 50% inhibition was approx. 10 −8 M; inhibition was completely blocked by a pertussis toxin. Prostaglandin E 2 had the same effect as dimethylprostaglandin E 2; prostaglandins D 2 and F 2α had no effect. Additions of sex hormones, 17β-estradiol and testosterone, and palmitic acid (diminishing the prostaglandin catabolism) to the culture medium did not change the effect of dimethylprostaglandin E 2. These data indicate that a sex difference exists in the inhibition of hepatic glycogenolysis by prostaglandin E 2 and its analogue in rat cultured hepatocytes, although the factor causing such a difference is at present unknown.