Hyperprolactinemia Induced by an Estrogen- Progesterone Synergy: Quantitative and Temporal Effects of Estrogen Priming in Monkeys*

We evaluated the quantitative and temporal characteristics of the estrogen component of an estrogen-progesterone synergy, which can induce hyperprolactinemia in macaques. In Exp I, six groups of monkeys were treated for 2 weeks with various doses of estradiol benzoate (EB), which resulted in peripheral estradiol concentrations of 250-1500 pg/ml, followed by 2 weeks of combined estrogen and progesterone treatment. In each of the groups, regardless of the dosages of estradiol benzoate alone, PRL concentrations remained within normal limits (approximately 18 ng/ml). In contrast, during the subsequent period of combined EB and progesterone therapy, hyperprolactinemia developed. The resultant PRL concentrations were not dependent on the dose of EB administered. In Exp II, three groups of monkeys were treated with EB (25 micrograms/kg) alone for various intervals and subsequently with both EB and progesterone for 14 days. When initiation of progesterone therapy was preceded by a 9- or 6-day period of estrogen priming, PRL concentrations were significantly (P less than 0.05) elevated within 3-4 days; in contrast, when the EB and progesterone treatments were initiated simultaneously, 8 days elapsed before the PRL elevations were significant. In a third experiment, to determine whether decidualized endometrium accounted for the increased PRL levels following estrogen and progesterone treatment, a hysterectomized monkey was treated with EB followed by combined EB and progesterone treatment. The PRL response was not different from that of intact monkeys similarly treated. From these findings we conclude 1) that the estrogen-progesterone synergy promoting PRL secretion is not of endometrial origin; 2) that approximately 1 week of estrogen priming is required for progesterone to induce PRL secretion; 3) and that the mode of action of estrogen is not dose dependent, but, rather, is a threshold effect.