PROLACTIN INCORPORATION CYCLE OF THE MILK SECRETORY-CELL - INTEGRAL COMPONENT OF THE PROLACTIN RESPONSE CYCLE

Endogenous prolactin (PRL) has previously been detected in the cytoplasm, and in some cases nuclei, of milk secretory cells (MSC) and other PRL target cells, using immunohistochemistry (IHC). This immunohistochemical method was used in the present study to compare the patterns of intracellular PRL (not PRL binding-sites) in MSC at different stages of their activity cycles. Flattened 'resting' MSC, lining the fully distended alveoli seen toward the end of a cycle, did not contain PRL, although PRL was present in luminal milk. With alveolar emptying, which initiates a new cycle, 'resting' cells are rapidly transformed into tall columnar cells. These 'active' MSC contained heterogeneous clusters of PRL in various cytoplasmic loci, a picture suggesting discontinuous redistribution of the internalized hormone. In about a fourth of these columnar MSC, PRL was also found in the nucleus. As the alveoli refill, these MSC regress in height and become cuboidal. Cuboidal cells showed no nuclear staining and their cytoplasmic PRL was rather uniformly dispersed, suggesting that internalization and transcellular transport of the hormone had become continuous. When alveolar filling is complete, the MSC reassume their flattened, PRL-negative 'resting' form. The cycle of PRL incorporation into MSC suggests certain functional correlates. It is clear that cytoplasmic incorporation of PRL is necessary for the transcellular transport of this hormone into the milk. However, this would not also require PRL entry into nuclei. The fact that nuclear incorporation was restricted to tall columnar MSC suggests that cycle initiation may involve direct actions of PRL on transcription. In addition, the prolonged sojourn of PRL in MSC cytoplasm, which extends throughout the active stages of the milk secretory cycle, would provide ample opportunity for PRL to exert direct actions on posttranscriptional events.