Endocrine secretion in vitro: prolactin.

In vitro studies on hormonal secretion by endocrine tissues can be of value in at least two ways. These isolated systems can serve as useful models for elucidating mechanisms of hormone biosynthesis and for analyzing the physiological interactions that regulate their manufacture, storage, and release. Recent studies on the production of prolactin by anterior pituitary in vitro provide an excellent example of the potentialities of this experimental approach. It is now generally recognized that the secretion and release of prolactin, like all anterior pituitary hormones, are regulated by the hypothalamus (1, 2). In contrast to other trophins, however, whose secretion is normally dependent upon hypothalamic stimulation, prolactin secretion appears to be chronically depressed by the nervous system. Thus, interruption of the neurohumoral connections between the anterior pituitary and the hypothalamus severely impairs the production of all adenohypophysial hormones, except for prolactin, whose secretion is augmented. From the evidence accumulated in several laboratories, the view has emerged that the adenohypophysis is controlled by six hypothalamic factors ("hypothalamic releasing factors"), which are released into the hypophysial portal system, one for each of the anterior lobe hormones (3). Five of them cause the release of the appropriate hormone, whereas the sixth inhibits the secretion of prolactin. This unique aspect of prolactin regulation by the nervous system has stimulated intensive research in recent years, both in vivo and in vitro (1, 2, 4, 5). Thus far, the sole exception to the general phenomenon of hypothalamic inhibition is encountered in birds, in which prolactin secretion appears to depend upon a stimulatory influence from the nervous system (6, 7). The possibility of other control mechanisms is thus raised, wherein the net effect would be a stimulation rather than an inhibition of prolactin secretion. There is, in fact, ample evidence that prolactin secretion can be stimulated by means other than disruption of hypothalamohypophysial connections. For example, several hormones (estrogen, progesterone, testosterone, cortisol, cortisone, epinephrine, norepinephrine), a wide variety of pharmacologic and nonspecific agents, and in some mammals at least, the suckling stimulus are all capable of augmenting the secretion of prolactin (4). The effects of some of these agents are thought to be mediated through the hypothalamus, presumably by inhibiting the inhibitory factor; others are thought to act by direct stimulation of the anterior pituitary. Cultures of anterior pituitary provide a number of experimental advantages that are otherwise difficult to achieve by animal experimentation alone. First, the in vitro system allows complete isolation of the anterior pituitary from all systemic influences, both stimulatory and inhibitory. Second, prolactin content and release can be readily measured in vitro as a function of time. Third, a variety of substances can be added to the cultures and their in'Recipient of USPHS Research Career Development Award and supported by USPHS grant HD-02374. 2 Supported as a Special Fellow of the USPHS at the Institute of Endocrinology, Gunma University, Maebashi, Japan, and in part by USPHS grant AM-06918.