Prolactin Regulation of Casein Gene Expression: Possible Mediators*

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Abstract
The role of polyamines and cyclic nucleotides as possible mediators of PRL action on casein gene expression has been studied in mammary gland organ culture. The concentration of casein mRNA in insulin and hydrocortiso,ne-treated cultures was decreased upon the addition of spermidine (0.5 mm), whereas when added with insulin alone this polyamine maintained casein mRNA levels similar to those observed in the insulin and hydrocortisone control. The addition of an inhibitor of spermidine synthesis (methylglyoxal bis guanylhydrazone) with PRL decreased the level of casein mRNA, but this effect could not be reversed by the simultaneous addition of spermidine. cGMP, whether in combination with spermidine or alone, when added with insulin and hydrocortisone resulted in a 1.3- to 2.3-fold elevation of casein mRNA levels. This approximate 2- fold response was specific for cGMP and could not be duplicated by butyric acid, GMP, 8-Br-GMP, cAMP, cCMP, or cUMP. This was in contrast to the 6- to 22-fold induction usually observed 24 h after PRL addition. In an attempt to directly stimulate endogenous cyclic nucleotide synthesis, prostaglandin E2, prostaglandin F2α, vasopressin, or oxytocin was added to the organ culture. None of these hormones was able to duplicate the effect of PRL on casein mRNA accumulation. Therefore, PRL regulation of the casein gene expression may be a complex process and is not directly mimicked by the addition of exogenous cyclic nucleotides or polyamines. (Endocrinology106: 252, 1980)