Nappi R E, Petraglia F, Guo A L, Criscuolo M, Trentini G P, Genazzani A R
Department of Obstetrics and Gynecology, University of Pavia, Italy.
Gynecol Endocrinol. 1996 Apr;10(2):75-82. doi: 10.3109/09513599609097895.
Corticotropin-releasing factor (CRF), the major regulator of the stress response within the central nervous system, is also present at peripheral sites, including the gonads, and the gene encoding its own receptor can be finely induced in selective ovarian compartments in both control and stressful conditions during the gonadal life cycle. The present study, therefore, investigated the influence of both gonadal function and estrous cycle on the immunoreactive CRF (irCRF) contents in the immature and adult rat ovary. In addition, the effect of an acute (5 min) or chronic intermittent (twice a day for 4 days) cold swimming stress on ovarian irCRF contents was evaluated. High-performance liquid chromatography (HPLC), gel-chromatography (Sephadex G-75, 45 x 1 cm) and a direct radioimmunoassay were performed to measure irCRF ovarian contents. The HPLC elution profile of irCRF in ovarian tissues of adult rats was superimposable on that of synthetic rat/human CRF and gel-chromatograms performed according to the phase of the estrous cycle revealed higher irCRF contents at proestrus. Total irCRF ovarian content was undetectable both in control and acute stressed immature rats, while adult rats showed the highest values at proestrus (p < 0.0001). The acute stress exposure induced a significant increase (p < 0.0001) of irCRF ovarian contents only at proestrus, without affecting irCRF at the other phases of the estrous cycle. Finally, no significant changes were found in ovarian irCRF after chronic intermittent stress. The proestrus-related changes of ovarian irCRF, confirming the adult ovary as an extrahypothalamic source of CRF, may constitute a neuropeptidergic signal involved in the gonadal reproductive cycle. Furthermore, the stress-related changes of ovarian irCRF indicated that the gonad may be locally sensitive to acute stressful stimuli.
促肾上腺皮质激素释放因子（CRF）是中枢神经系统内应激反应的主要调节因子，在包括性腺在内的外周部位也有存在，并且在性腺生命周期的对照和应激条件下，其自身受体的编码基因可在选择性卵巢区室中被精细诱导。因此，本研究调查了性腺功能和发情周期对未成熟和成年大鼠卵巢中免疫反应性CRF（irCRF）含量的影响。此外，评估了急性（5分钟）或慢性间歇性（每天两次，持续4天）冷游泳应激对卵巢irCRF含量的影响。采用高效液相色谱（HPLC）、凝胶色谱（Sephadex G - 75，45×1 cm）和直接放射免疫测定法来测量卵巢中irCRF的含量。成年大鼠卵巢组织中irCRF的HPLC洗脱图谱与合成的大鼠/人类CRF的图谱重叠，根据发情周期阶段进行的凝胶色谱图显示，发情前期的irCRF含量更高。在对照和急性应激的未成熟大鼠中均未检测到卵巢总irCRF含量，而成年大鼠在发情前期显示出最高值（p < 0.0001）。急性应激暴露仅在发情前期诱导卵巢irCRF含量显著增加（p < 0.0001），而在发情周期的其他阶段不影响irCRF含量。最后，慢性间歇性应激后卵巢irCRF未发现显著变化。卵巢irCRF与发情前期相关的变化，证实成年卵巢是CRF的下丘脑外来源，可能构成参与性腺生殖周期的神经肽信号。此外，卵巢irCRF与应激相关的变化表明性腺可能对急性应激刺激具有局部敏感性。
