Fora M A, Butler T G, Rose J C, Schwartz J
Department of Physiology, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27157, USA.
Endocrinology. 1996 Aug;137(8):3394-400. doi: 10.1210/endo.137.8.8754766.
Immunoreactive (ir) ACTH is present in the fetal sheep intermediate lobe (IL) as well as the anterior pituitary (AP). It is not clear whether fetal IL cells can secrete irACTH and if gestational age and glucocorticoids influence the secretion of ACTH from these tissues in a similar fashion. Therefore, we examined the control of irACTH secretion by IL cells, whether the responsiveness of AP and IL cells to arginine vasopressin (AVP) and CRH changes during gestation, and whether withdrawal of adrenal steroids by adrenalectomy influences AP and IL responses. Cultured pituitary cells were studied from intact fetuses at an immature (n = 5; 108 +/- 5 days) and a mature (n = 8; 139 +/- 0 days) stage, from mature fetuses 3 weeks after bilateral adrenalectomy (n = 6), and from neonatal lambs within 16 h of birth (n = 6). Secretion of irACTH was determined by RIA of incubation medium obtained during 3-h exposure of cells to vehicle, AVP, CRH, or both. In all cases, IL cells secreted measurable irACTH. The IL cells of immature fetuses responded to CRH (133 +/- 8% increase over basal secretion), AVP (52 +/- 6%), and CRH plus AVP (244 +/- 8%). In contrast, IL cells from mature fetuses responded only to CRH (160 +/- 20%) or CRH plus AVP (259 +/- 44%), as did cells from mature adrenalectomized fetuses (CRH, 356 +/- 70%; CRH plus AVP, 627 +/- 100%). Secretion from neonatal IL cells was not significantly increased above basal rates by CRH and/or AVP. The AP cells from immature fetuses responded significantly to CRH (406 +/- 16%), AVP (114 +/- 8%), and CRH plus AVP (559 +/- 38%), whereas cells from mature fetuses responded only to AVP (249 +/- 40%) or to CRH plus AVP (570 +/- 146%). In AP cells from mature adrenalectomized fetuses, the response pattern resembled that of immature intact fetal sheep (CRH, 429 +/- 76%; AVP, 146 +/- 15%; CRH plus AVP, 541 +/- 94%). Neonatal AP cells responded to CRH (196 +/- 25%), AVP (442 +/- 71%), and CRH plus AVP (646 +/- 93%). Further characterization of IL cells (n = 6 fetal and 2 neonatal) indicated that they were inhibited by dopamine (basal ACTH secretion decreased by 25 +/- 4%; ACTH secretory response to CRH decreased by 32 +/- 10%). These results show that fetal neurointermediate lobe cells secrete irACTH under basal and stimulated conditions. Moreover, the pattern of response of AP and neurointermediate lobe cells to secretagogues is influenced by gestational age and, possibly, cortisol.
免疫反应性（ir）促肾上腺皮质激素（ACTH）存在于胎羊的中间叶（IL）以及垂体前叶（AP）中。目前尚不清楚胎儿IL细胞是否能分泌irACTH，以及胎龄和糖皮质激素是否以类似方式影响这些组织中ACTH的分泌。因此，我们研究了IL细胞对irACTH分泌的控制，AP和IL细胞对精氨酸加压素（AVP）和促肾上腺皮质激素释放激素（CRH）的反应性在孕期是否发生变化，以及肾上腺切除术去除肾上腺类固醇是否会影响AP和IL的反应。我们研究了来自未成熟（n = 5；108±5天）和成熟（n = 8；139±0天）阶段的完整胎儿、双侧肾上腺切除术后3周的成熟胎儿（n = 6）以及出生后16小时内的新生羔羊（n = 6）的培养垂体细胞。通过放射免疫分析法（RIA）测定细胞在3小时内分别暴露于溶剂、AVP、CRH或两者时获得的孵育培养基中的irACTH分泌量。在所有情况下，IL细胞均分泌可测量的irACTH。未成熟胎儿的IL细胞对CRH（比基础分泌增加133±8%）、AVP（52±6%）以及CRH加AVP（244±8%）有反应。相比之下，成熟胎儿的IL细胞仅对CRH（160±20%）或CRH加AVP（259±44%）有反应，成熟肾上腺切除胎儿的细胞也是如此（CRH，356±70%；CRH加AVP，627±100%）。CRH和/或AVP并未使新生IL细胞的分泌量显著高于基础水平。未成熟胎儿的AP细胞对CRH（406±16%）、AVP（114±8%）以及CRH加AVP（559±38%）有显著反应，而成熟胎儿的细胞仅对AVP（249±40%）或CRH加AVP（570±146%）有反应。成熟肾上腺切除胎儿的AP细胞的反应模式类似于未成熟完整胎儿（CRH，429±76%；AVP，146±15%；CRH加AVP，541±94%）。新生AP细胞对CRH（196±25%）、AVP（442±71%）以及CRH加AVP（646±93%）有反应。对IL细胞（n = 6个胎儿和2个新生）的进一步特性分析表明，它们受到多巴胺的抑制（基础ACTH分泌减少25±4%；对CRH的ACTH分泌反应减少32±10%）。这些结果表明，胎儿神经中间叶细胞在基础和刺激条件下均分泌irACTH。此外，AP和神经中间叶细胞对促分泌素的反应模式受胎龄影响，可能还受皮质醇影响。
