PARACRINE INTERACTIONS IN PROLACTIN SECRETION

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Various paracrine peptides are released in the anterior pituitary (AP) gland and seem to play an important role in regulating secretory activity of PRL cells. Depending upon its inhibitory or stimulatory influence, the peptide may cause lactotrophs to secrete varied amount of PRL. Such a functional heterogeneity has been observed in PRL cells based upon their size, density as well as their location within the AP gland. We have shown that synthetic salmon calcitonin (sCT) selectively inhibits basal and TRH-stimulated PRL release and reduces basal and TRH- induced cytoplasmic mRNA levels in cultured AP cells. The action of sCT is at least potent as dopamine, while CGRP is much less effective, suggesting a specific role for sCT or a closely related endogenous peptide (pCT) in regulation of PRL secretion. Our recent studies suggest that sCT-like immunoreactive peptide (pCT) is synthesized and secreted by cultured AP cells and the immunoneutralization with anti-sCT serum causes a significant increase in PRL release from cultured AP cells and in serum PRL levels in neonatal rats. These findings suggest that pCT may be an important paracrine inhibitor of PRL release. Initial studies in hemi-dissected AP glands indicate that pCT is predominantly released from the caudal section, and this section also has low PRL mRNA content and secretes lesser amounts of PRL. These results suggest that the presence of pCT may be one of the important mechanism for low PRL transcriptional and secretory activity in the caudal section. The objective of the present proposal is to test the hypothesis that pCT is a physiologically important local paracrine regulator of PRL secretion in adult rats, and in concert with other factors, contributes to the functional heterogeneity of lactotrophs. The first Specific Aim of this proposal will examine whether pCT exerts a location-dependent paracrine influence of PRL release and synthesis. Specific Aim 2 will identify the pituitary cell type(s) that secrete pCT and examine their anatomical association with lactotrophs. Specific Aim 3 will examine anatomical distribution of sCT-binding sites in the AP gland and their regulation by steroid hormones. Specific Aim 4 will investigate whether regulators of PRL secretion modulate pCT release, and Specific Aim 5 will obtain a pCT cDNA for determination of the primary pCT sequence and obtain a cDNA probe for pCT in situ hybridization histochemistry. The proposed studies will attempt to define the physiological role for the pCT in paracrine regulation of PRL secretion, and its contribution to the functional heterogeneity of PRL cells and overall functioning of the AP gland.