PARACRINE INTERACTIONS IN PROLACTIN SECRETION

各种旁分泌肽在垂体前叶（AP）释放 腺，并似乎在调节分泌的重要作用 PRL细胞的活性。 取决于它的抑制或刺激 影响，该肽可以引起催乳素分泌不同量的 催乳素 这种功能异质性已在PRL细胞中观察到 根据它们的大小、密度以及它们在AP内的位置 腺。 我们已经表明，合成鲑鱼降钙素（sCT）选择性 抑制基础和TRH刺激的PRL释放，减少基础和TRH- 诱导培养的AP细胞的胞质mRNA水平。 sCT的作用 至少和多巴胺一样有效，而CGRP的效果要差得多， 提示sCT或密切相关的内源性 肽（pCT）调节PRL分泌。 我们最近的研究 提示合成了sCT样免疫反应肽（pCT）， 培养的AP细胞分泌的抗体和抗sCT的免疫中和 血清引起培养AP的PRL释放显著增加 细胞和血清PRL水平。 这些发现表明 pCT可能是PRL释放的重要旁分泌抑制剂。 在半解剖AP腺体中的初步研究表明，pCT是 主要从尾部释放，并且该部分也 具有低PRL mRNA含量并且分泌较少量的PRL。 这些 结果表明，pCT的存在可能是重要的 低PRL转录和分泌活性的机制 尾部 本提案的目的是测试 假设pCT是生理上重要局部旁分泌 在成年大鼠的PRL分泌调节剂，并与其他 因素，有助于催乳素的功能异质性。 该提案的第一个具体目标将审查pCT是否发挥 PRL释放和合成的位置依赖性旁分泌影响。 具体目标2将鉴定分泌pCT的垂体细胞类型 并检查它们与催乳素的解剖学联系。 具体目标 3将检查AP中sCT结合位点的解剖分布 腺体及其受类固醇激素的调节。 具体目标4将 研究PRL分泌调节剂是否调节pCT释放， 和特异性目的5将获得pCT cDNA，用于测定 一级pCT序列，并原位获得pCT的cDNA探针 杂交组织化学 拟议中的研究将试图确定的生理作用， 催乳素旁分泌调节中pCT及其作用 PRL细胞的功能异质性和 AP腺

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.