Prolactin–progesterone antagonism in self regulation of prolactin receptors in the mammary gland

Abstract

THE role of prolactin during growth of the mammary gland and in lactation is well established (see ref. 1 for review) and the antagonising action of progesterone on lactogenesis (but not on mammary growth) has been recognised^2–4. A specific receptor for prolactin has been described⁵ and purified⁶ and it seems that the level of this receptor in the target cells is very sensitive to hormonal environments and might be one of the essential parameters which modulates the intensity of prolactin action. Titration of this receptor under controlled hormonal conditions has been mainly performed in the liver and its concentrations found to be sensitive to oestrogens⁷; this effect may be amplified or even mediated by prolactin itself⁸. We have shown⁹ that the number of prolactin receptors in the mammary gland of pregnant or lactating rabbits undergoes a sudden increase at the onset of lactation but that the K_a of the receptor–hormone interaction remains constant. The question arises as to which hormonal environment is required for this amplification; is the inhibitory action of high progesterone levels on lactogenesis associated with a reduction of receptor concentrations? We describe here a study of this possibility and of the positive regulation of prolactin on its own receptors in the rabbit mammary gland. We extend to the mammary gland the stimulating effect of prolactin on the levels of its receptors and demonstrate an antagonising action of progesterone on this process.