GENOMIC AND NON-GENOMIC ACTIONS OF PROGESTERONE IN THE CONTROL OF FEMALE HAMSTER SEXUAL-BEHAVIOR
GENOMIC AND NON-GENOMIC ACTIONS OF PROGESTERONE IN THE CONTROL OF FEMALE HAMSTER SEXUAL-BEHAVIOR
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DOI：
10.1006/hbeh.1994.1042
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发表时间：
1994-12-01
影响因子：
3.5
通讯作者：
FRYE, CA
中科院分区：
文献类型：
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作者：
DEBOLD, JF;FRYE, CA
下丘脑腹内侧区(VMH)和腹侧被盖区(VTA)中的基因组孕酮(P)是促进雌激素诱导的仓鼠性接受所必需的。在VMH和VTA，P的作用机制可能不同，VMH细胞内孕激素受体(PR)较多，VTA细胞内孕激素受体(PR)较少。与牛血清白蛋白(P-3-BSA)结合的孕酮不能很好地与细胞内PR结合，也不能很好地渗透神经细胞膜。然而，如果在VMH较早地应用P-3-BSA，则VTA应用P-3-BSA可迅速增强性接受性。P-S-牛血清白蛋白应用于VMH无效。P的膜限制作用可能与某些孕激素调节GABA(A)-苯二氮卓受体复合体(GBRC)的能力有关。我们已经发现，向VTA内注入GABA(A)激动剂Muscimol可以增强VTA的感受性，而GABA(A)拮抗剂荷包牡丹碱则抑制感受性。由于P本身在GBRC中不是很有效，而且GBRC中最有效的调节剂-5α-还原型孕激素不能很好地与PR结合，孕激素代谢物被应用于VTA。只有有效的GBRC调节剂与P同时作用于VTA和VMH时，才促进了性感受性。将孕激素代谢物植入VMH的反向治疗无效。VTA注入5α-还原酶抑制剂也减弱了金黄地鼠的行为发情。这些数据与在VMH中P易化的性感受是一致的，而在VTA中P的非基因组作用可能是代谢和随后与GBRC相互作用的结果。(C)1994年学术出版社。
Genomic Progesterone (P) in both the ventromedial hypothalamus (VMH) and the ventral tegmental area (VTA) is necessary to facilitate sexual receptivity in estrogen-primed hamsters. The mechanism of P may be different in the VMH and VTA, as there are many intracellular progestin receptors (PR) in the VMH but few in the VTA. Progesterone conjugated to bovine serum albumin (P-3-BSA) does not bind well to intracellular PR or permeate the surface of neuronal membranes. However, VTA application of P-3-BSA rapidly increases sexual receptivity if P has been applied earlier to the VMH. P-S-BSA is ineffective when applied to the VMH. The membrane-limited effect of P may be related to the ability of some progestins to modulate the GABA(A)-benzodiazepine receptor complex (GBRC). We have found that infusions of a GABA(A) agonist, muscimol, into the VTA enhance and a GABA(A) antagonist, bicuculline, inhibit receptivity. Because P itself is not highly effective at the GBRC, and since the most potent modulators of the GBRC, the 5 alpha-reduced progestins, do not bind well to PRs, progestin metabolites were applied to the VTA. Only the potent GBRC modulators facilitated sexual receptivity when applied to the VTA concurrent with P to the VMH. The reverse treatment, with a progestin metabolite implanted into the VMH, was ineffective. VTA infusions of an inhibitor of 5 alpha-reductase also attenuated behavioral estrus in hamsters. These data are consistent with P facilitation of sexual receptivity being genomically mediated in the VMH, while the non-genomic actions of P in the VTA may be a result of metabolism and subsequent interaction with the GBRC. (C) 1994 Academic Press, Inc.