STUDIES OF THE REGULATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN SHEEP WITH HYPOTHALAMIC-PITUITARY DISCONNECTION .2. EVIDENCE FOR INVIVO ULTRADIAN HYPERSECRETION OF PROOPIOMELANOCORTIN PEPTIDES BY THE ISOLATED ANTERIOR AND INTERMEDIATE PITUITARY
STUDIES OF THE REGULATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN SHEEP WITH HYPOTHALAMIC-PITUITARY DISCONNECTION .2. EVIDENCE FOR INVIVO ULTRADIAN HYPERSECRETION OF PROOPIOMELANOCORTIN PEPTIDES BY THE ISOLATED ANTERIOR AND INTERMEDIATE PITUITARY
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DOI：
10.1210/endo-127-4-1956
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发表时间：
1990-10-01
期刊：
影响因子：
4.8
通讯作者：
FUNDER, JW
中科院分区：
文献类型：
--
作者：
ENGLER, D;PHAM, T;FUNDER, JW
我们进行了研究，以确定分离的羊垂体前叶和中间叶是否有节律地分泌三种POMC肽、ACTH、ir- β。内啡肽(ir度量。-EP)和- α。-促黑素细胞激素（ir-. α .- msh）当4只患有下丘脑-垂体-断连（HPD）的母羊每隔10分钟采血时，可以注意到明显的pomc肽和皮质醇超节律。将4只HPD母羊与5只未应激的HPI母羊进行比较，发现3种pomc肽和皮质醇的平均血浆水平升高，平均ACTH和ir- α升高。-MSH脉冲振幅增大，平均ir-。-EP和- α。-MSH脉间间隔缩短。当4只HPI母羊受到轻度应激时，与5只未受应激的HPI母羊相比，血浆pomc肽和皮质醇水平显著升高。ACTH和皮质醇脉搏幅值升高，ir- β。-EP和- α。-MSH脉冲间隔缩短。虽然应激HPI和HPD母羊的血浆ACTH水平相当，但应激HPI母羊的平均血浆皮质醇水平高出2倍。为了确定HPD母羊的ACTH高分泌是否反映了下丘脑对ACTH分泌的抑制作用的净减少，我们检测了多巴胺（DA）、生长抑素（SS-14）和大鼠心房利钠肽[rANF(1-28)]对培养的羊垂体前叶细胞ACTH分泌的影响。DA和SS-14对基础、CRF-或精氨酸抗利尿激素（AVP）刺激的ACTH分泌没有明显影响。虽然基底ACTH分泌不受rANF(1-28) （10-12-10-8 M）的影响，但观察到CRF和avp刺激的ACTH释放受到显著抑制。此外，当100亩。g通过颈外动脉注射rANF（1-28）给4只HPD母羊，血浆ACTH和皮质醇的升高与注射NaCl的4只HPD母羊没有差异。我们得出结论：1)脉冲性pomc肽分泌是促肾上腺皮质激素和促黑色素激素的内在特性；2) HPI母羊体内pomc肽的分泌反映了下丘脑对垂体内在节律的改变；3)在HPI母羊中，轻度应激激活下丘脑使血浆ACTH升高至HPD母羊的水平，并增加ACTH脉冲频率和脉冲幅度；4)血浆ir- β水平升高。-EP和- α。-MSH和ir- β降低。- HPD后ep脉间间隔提示神经输入中间叶抑制中间叶pomc肽分泌；5) HPD后血浆ACTH和皮质醇水平升高提示下丘脑对垂体前叶的POMC肽合成和/或分泌也有强直性抑制作用；然而，这种假定的抑制影响不是由多巴胺或SS-14介导的；6) ANF（1-28）在体外抑制CRF或avp介导的ACTH分泌的能力表明，羊促肾上腺皮质激素可能具有抑制ACTH分泌的细胞内机制，与介导糖皮质激素反馈作用的机制不同。
Studies were performed to determine whether the isolated ovine anterior and intermediate pituitary, might rhythmically secrete three POMC peptides, ACTH, ir-.beta.-endorphine (ir-.beta.-EP), and ir-.alpha.-melanocyte stimulating hormone (ir-.alpha.-MSH) in vivo. When blood was taken at 10-min intervals from four ewes with hypothalamo-pituitary-disconnection (HPD), a distinct POMC-peptide and cortisol ultradian rhythm was noted. A comparison of the four HPD ewes with five nonstressed hypothalamopituitary-intact (HPI) ewes revealed that the mean plasma levels of the three POMC-peptides and cortisol were increased, the mean ACTH and ir-.alpha.-MSH pulse amplitudes were increased, and the mean ir-.beta.-EP and ir-.alpha.-MSH interpulse intervals were decreased. When four HPI ewes were subjected to a mild stress, plasma POMC-peptide and cortisol levels increased significantly when compared with the five unstressed HPI animals. In addition, the ACTH and cortisol pulse amplitudes increased and the ir-.beta.-EP and ir-.alpha.-MSH interpulse intervals decreased. Although plasma ACTH levels in the stressed HPI and HPD ewes were comparable, mean plasma cortisol levels were 2-fold greater in the stressed HPI animals. To determine whether the ACTH hypersecretion in the HPD ewe might reflect a net reduction in hypothalamic inhibitory influence over ACTH secretion, we examined the effects of dopamine (DA) somatostatin (SS-14), and rat atrial natriuretic peptide [rANF(1-28)] on the secretion of ACTH from cultured ovine anterior pituitary cells. DA and SS-14 did not exert a discernible effect on basal, CRF-, or arginine vasopressin (AVP)-stimulated ACTH secretion. Although basal ACTH secretion was unaffected by rANF(1-28) (10-12-10-8 M), a significant inhibition of CRF- and AVP-stimulated ACTH release was observed. Furthermore, when 100 .mu.g rANF(1-28) was injected via the external carotid artery into four HPD ewes, the rise in plasma ACTH and cortisol did not differ from that seen in four HPD ewes injected with NaCl. We conclude that: 1) pulsatile POMC-peptide secretion is an intrinsic property of the corticotrope and melanotrope; 2) POMC-peptide secretion in the HPI ewe represents the modification of this intrinsic pituitary rhythm by the hypothalamus; 3) in the HPI ewe, activation of the hypothalamus by mild stress increases plasma ACTH to levels seen in the HPD ewe, and increases both the ACTH pulse frequency and pulse amplitude; 4) the increased plasma levels of ir-.beta.-EP and ir-.alpha.-MSH and decreased ir-.beta.-EP interpulse interval after HPD suggests that the neural input to the intermediate lobe restrains intermediate lobe POMC-peptide secretion; 5) the increased plasma ACTH and cortisol levels after HPD suggests that the hypothalamus also exerts a tonic inhibitory influence over POMC peptide synthesis and/or secretion by the anterior pituitary; however, this putative inhibitory influence is not mediated by dopamine or SS-14; 6) the ability of ANF(1-28) to inhibit CRF- or AVP-mediated ACTH secretion in vitro suggests that the ovine corticotrope may possess intracellular mechanisms that inhibit ACTH secretion which are distinct from those which mediate the feedback actions of the glucocorticoids.