High levels or long periods of stress have been shown to negatively impact cell homeostasis, including with respect to abnormalities in domestic animal reproduction, which are typically activated through the hypothalamus–pituitary–adrenal axis, in which corticotropin-releasing hormone (CRH) and heat shock protein 70 (HSP70) are involved. In addition, CRH has been reported to inhibit pituitary gonadotrophin synthesis, and HSP70 is expressed in the pituitary gland. The aim of this study was to determine whether HSP70 was involved in regulating gonadotrophin synthesis and secretion by mediating the CRH pathway in the porcine pituitary gland. Our results showed that HSP70 was highly expressed in the porcine pituitary gland, with over 90% of gonadotrophic cells testing HSP70 positive. The results of functional studies demonstrated that the HSP70 inducer decreased FSH and LH levels in cultured porcine primary pituitary cells, whereas an HSP70 inhibitor blocked the negative effect of CRH on gonadotrophin synthesis and secretion. Furthermore, our results demonstrated that HSP70 inhibited gonadotrophin synthesis and secretion by blocking GnRH-induced SMAD3 phosphorylation, which acts as the targeting molecule of HSP70, while CRH upregulated HSP70 expression through the PKC and ERK pathways. Collectively, these data demonstrate that HSP70 inhibits pituitary gonadotrophin synthesis and secretion by regulating the CRH signaling pathway and inhibiting SMAD3 phosphorylation, which are important for our understanding the mechanisms of the stress affects domestic animal reproductive functions.

高水平或长时间的压力已被证明会对细胞稳态产生负面影响，包括家畜繁殖异常，这些异常通常通过下丘脑 - 垂体 - 肾上腺轴激活，其中促肾上腺皮质激素释放激素 (CRH) 和热量休克蛋白 70 (HSP70) 参与其中。此外，据报道 CRH 可抑制垂体促性腺激素的合成，HSP70 在垂体中表达。本研究的目的是确定 HSP70 是否通过介导猪垂体中的 CRH 途径参与调节促性腺激素合成和分泌。我们的结果表明，HSP70 在猪脑垂体中高表达，超过 90% 的促性腺细胞检测 HSP70 呈阳性。功能研究的结果表明，HSP70 诱导剂降低了培养的猪原代垂体细胞中的 FSH 和 LH 水平，而 HSP70 抑制剂阻止了 CRH 对促性腺激素合成和分泌的负面影响。此外，我们的结果表明，HSP70 通过阻断 GnRH 诱导的 SMAD3 磷酸化来抑制促性腺激素的合成和分泌，SMAD3 作为 HSP70 的靶向分子，而 CRH 通过 PKC 和 ERK 途径上调 HSP70 的表达。总的来说，这些数据表明 HSP70 通过调节 CRH 信号通路和抑制 SMAD3 磷酸化来抑制垂体促性腺激素的合成和分泌，这对于我们理解应激影响家畜生殖功能的机制很重要。