PARACRINE INTERACTIONS IN PROLACTIN SECRETION

各种旁分泌多肽在垂体前叶(AP)释放。 腺体，似乎在调节分泌方面起着重要作用 PRL细胞活性。取决于它的抑制性或刺激性 影响，该肽可能会导致乳酸菌分泌不同数量的 PRL.在PRL细胞中观察到了这样的功能异质性 根据它们的大小、密度以及它们在AP中的位置 腺体。我们已经证明合成鲑鱼降钙素(SCT)具有选择性 抑制基础和TRH刺激的PRL释放，减少基础和TRH- 诱导培养的AP细胞胞浆内的mRNA水平。SCT的作用 至少和多巴胺一样有效，而降钙素基因相关肽的作用要小得多， 提示SCT的特定作用或密切相关的内源性 调节催乳素分泌的多肽(PCT)。我们最近的研究 提示合成了SCT样免疫反应肽(PCT)，并 培养的AP细胞分泌及抗SCT免疫中和作用 血清可显著增加培养的AP分泌催乳素 新生大鼠血清中催乳素水平。这些发现表明 PCT可能是PRL释放的重要旁分泌抑制物。 对半切AP腺体的初步研究表明，PCT是 主要从尾部松开，这一部分也 PRL mRNA含量较低，分泌的PRL较少。这些 结果表明，PCT的存在可能是 小鼠PRL转录和分泌活性低的机制 尾部切开。本提案的目的是测试 假设PCT是一种生理上重要的局部旁分泌 成年大鼠催乳素分泌的调节及与其他激素的协同作用 因素，有助于乳酸菌功能的异质性。 这项提案的第一个具体目标将审查PCT是否发挥了 位置依赖的旁分泌对PRL释放和合成的影响。 特定目标2将确定分泌pct的脑垂体细胞类型(S) 并研究它们与乳酸菌的解剖学联系。特定目标 3将研究AP中SCT结合部位的解剖分布。 腺体及其类固醇激素的调节。具体目标4将 研究PRL分泌调节剂是否调节PCT的释放， 和特定目标5将获得用于测定 对PCT进行初步测序，获得用于PCT原位杂交的cDNA探针 杂交组织化学。 拟议中的研究将试图定义大脑的生理作用 PCT在旁分泌调节催乳素分泌中的作用 与PRL细胞的功能异质性和PRL的整体功能 AP腺体。

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.