Abstract
Abstract The secretion of prolactin by the pituitary gland is under a tonic inhibitory control exerted by tubero-infundibular dopamine. Recently, it has been suggested that dopamine may exert its action by inhibiting production of inositol phosphates and mobilization of intracellular Ca(2+). To study the effects of dopamine on the production of inositol phosphates and prolactin release, we have utilized an estrone-induced, dopamine-sensitive rat pituitary adenoma and two transplantable and dopamine-resistant rat pituitary tumors, 7315a and MtTW15. Purified cells, obtained from the three tissues, were incubated for 30 min in media with drugs (thyrotropin-releasing hormone or angiotensin II) stimulating inositol phosphates and prolactin release, in the presence or the absence of dopamine. Basal production of inositol phosphates and prolactin release by adenomatous lactotrophs were inhibited by dopamine. Thyrotropin-releasing hormone and angiotensin II stimulated inositol phosphates by adenomatous and 7315a cells. This effect was antagonized by dopamine in adenomatous cells. Prolactin release by adenomatous cells only was stimulated by thyrotropin-releasing hormone and angiotensin II. This stimulation was inhibited by dopamine. The results show differences, in the mechanisms of regulation of prolactin release, between adenoma and transplantable pituitary tumors as well as between the two tumors themselves. These differences may be responsible, in part, for the resistance of the two transplantable pituitary tumors to the inhibitory effects of dopamine on prolactin release and tumor size. Our results obtained both with adenoma and tumoral cells also suggest that inositol phosphates probably intervene only in the late phases of dopamine inhibition of prolactin release and only in the presence of a normal Ca(2+) signaling system.
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