8. Steroids and differentiation. The role of estrogen in the differentiation of prolactin producing cells.

The capacity to synthesize PRL and GH was studied in normal mice and in Snell and Ames dwarfs. In normal mice GH synthesis turned on dramatically between day 16-17 of gestation whereas PRL was not detectable throughout gestation or the first week of life, was barely detectable in 8-day-old mice and was clearly demonstrable by 12 days of age. However, transplantation of pituitaries from newborn mice into adult female hosts resulted in substantial PRL synthesis. Treatment of mice with DES at various ages showed that neonates failed to respond to the hormone; in older pups, an age-dependent increase in the magnitude of PRL synthesis was observed. There was a direct correlation between nuclear estrogen receptor levels and PRL cell function. Snell and Ames dwarf mice failed to synthesize PRL or GH at any stage of development, nor could we detect immunoreactive peptides which might represent mutant forms of the hormones. Our findings suggest that: (1) GH gene expression precedes that of PRL by about 2 weeks; (2) the development of PRL cell function is dependent on estrogen; (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; and (4) in Snell and Ames mutants, both types of alleles result in failure of the pituitary to initiate PRL and GH synthesis.