Hyperprolactinemia in monkeys: induction by an estrogen-progesterone synergy

To evaluate the synergistic effect of estrogens and progesterone on prolactin secretion, rhesus and cynomolgus monkeys in the early follicular phase received estradiol benzoate (100 microgram/kg/day, sc) alone for 14 days, then in combination with progesterone (subcutaneous silastic capsule) for an additional 14 days. Blood was drawn daily by femoral venipuncture under ketamine hydrochloride anesthesia (15 mg/kg). Similarly, this protocol for exogenous steroid treatment was employed in a monkey having a chronically indwelling (femoral insertion into the vena cava) cannula maintained by a vest and mobile tether apparatus; however, no anesthesia was used to obtain serum specimens. In addition, this assembly was applied to six monkeys to determine the acute effects of ketamine hydrochloride on prolactin secretion. Concentrations of prolactin, estradiol-17 beta, and progesterone in serum were determined by conventional radioimmunoassays. Under estrogen therapy alone, mean circulating prolactin levels declined from approximately 15 to less than 5 ng/ml; in contrast, the addition of progesterone caused an abrupt serum prolactin elevation, approximately 8-12 fold. This estradiol-progesterone course led to sustained hyperprolactinemia in the chronically catheterized monkey, whereas ketamine administration raised serum prolactin only briefly, the elevation lasting less than three hours after injection. These findings establish that an estrogen-progesterone synergy, separate from the transient effects of ketamine, induced hyperprolactinemia in cycling monkeys having prevailing levels of estrogen and progesterone near those characteristic of late gestation, when sustained prolactin elevations are observed normally.