Regulation of prolactin secretion by oestrogens: physiological and pathological significance.

Prolactin is unique among the anterior pituitary hormones in that it is under tonic inhibitory control by the hypothalamus. There is much evidence that the major prolactin inhibitory factor is dopamine [l-31. However, there are a number of physiological stimuli of prolactin secretion which can ‘override’ the effect of dopamine and one of the most important of these is oestrogen. Oestrogens are known to be involved in the physiological control of prolactin secretion in both rodent and primate [2,4]. Furthermore, exogenous oestrogens have long been known to induce prolactinsecreting pituitary tumours in certain strains of rat [5-71. In recent years there has been a resurgence of interest in the physiological and pathophysiological actions of oestrogen on prolactin secretion. This research has been prompted by the recognition that pathological hyperprolactinaemia (often associated with the presence of a pituitary tumour) presenting with disturbances in the menstrual cycle, is a common finding in women of reproductive age [8], thus raising the question of a role for endogenous oestrogens in the aetiology of hyperprolactinaemia. In the following pages I shall review the evidence for involvement of oestrogens in the physiological control of prolactin secretion, highlight recent studies bearing on the mechanism of oestrogen action on prolactin and discuss the implications of the effects of endogenous and exogenous oestrogens in the aetiology of hyperprolactinaemia in man. first delineated in the rat and has been reviewed by Neill [2]. Prolactin concentrations in the plasma are low before the onset of the fust oestrus cycle; after puberty they remain low during the cycle until the afternoon of pro-oestrus when there is a 10-fold increase in levels [9]. This ‘surge’ in prolactin is similar to that observed for luteinizing hormone (LH) and is preceded by a rapid increase in serum oestradiol concentrations. The pro-oestrus ‘surge’ of prolactin can be prevented by pre-treatment with an antiserum to oestradiol [ 101, thereby indicating that this dramatic rise in prolactin (which, in the rat, is important in the maintenance of the corpus luteum) is, indeed, oestrogen dependent. Oestrogen also appears to affect ‘non-surge’ levels of prolactin in that these low basal concentrations fall significantly lower after ovariectomy [ l l ] (to levels comparable with those of male rats), but can be restored by the administration of oestradiol. More recently, studies in man have confirmed the importance of oestrogen as a physiological prolactin-stimulating agent, although cyclical changes in prolactin levels are less clear-cut than in the rodent. Differences in basal prolactin concentrations between men and women are small and, in most studies, not statistically significant [12]. However, the prolactin response to exogenous thyrotrophin-releasing hormone is significantly greater in women than in men or prepubertal children [ 121. There remains some controversy regarding changes in serum prolactin concentrations during the menstrual cycle [13]. Some studies have shown no significant changes throughout the cycle [14-161 whilst others have demonstrated that prolactin levels are higher at the time of the Physiological regulation of prolactin secretion by oestrogen mid-cicle surge of LH than in the early follicular phase [ 13,17,18]. Because of the episodic nature of prolactin secretion these discrepancies may The importance of endogenous oestrogen in the physiological control of prolactin secretion was