Ontogeny of Growth Hormone and Prolactin Gene Expression in Mice*

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Abstract
The ontogeny of GH and PRL synthesis and the inducibility of PRL gene expression by estrogens during postnatal development in mice were studied. Synthetic rates were assessed by one- and two-dimensional gel electrophoresis and by immunoprecipitation of solubilized proteins from intact glands and monolayer cultures of pituitary cells labeled with [35S]methionine and [3H]leucine. We found that GH synthesis turns on dramatically between 16 and 17 days of gestation, comprising 15–20% of the total pituitary protein synthesis at birth. PRL synthesis was not detectable throughout gestation or in 1- to 4-day-old mice, and was barely detectable in 8-day-old mice. It was clearly demonstrable by 12 days of age and increased sharply thereafter, reaching 8–9% of the total protein synthesis by day 20 in both sexes. However, transplantation of pituitaries from newborns under the renal capsule of adult female hosts resulted in substantial PRL synthesis by the ectopic glands before the endogenous timetable. For studies of estrogenic induction of PRL synthesis, 1-, 5-, 10-, and 15-day-old mice were treated with 5 μg diethylstilbestrol for 3 days. Newborn pups failed to respond to the hormone; in older animals, an age-dependent increase in the magnitude of the response was observed. A similar pattern of induction was noted after the addition of 10 nM estradiol to monolayer cultures prepared from pituitaries of 1-, 6-, and 15-day-old mice. Translocatable nuclear estrogen receptors were measured in pituitaries of 1- to 28-day-old animals. Receptors per cell increased from approximately 900 on day 1 to 10,000 by day 28. There was a direct correlation between the nuclear receptor concentration and PRL cell function. Our findings suggest that 1) GH gene expression precedes that for PRL by about 2 weeks; 2) the development of PRL cell function is dependent on estrogen; and 3) the capacity to respond to estrogen is present before the endogenous initiation of PRL synthesis and is limited by the availability of estrogen receptor.