Reproductive functions may be affected by internal and external factors that are integrated in the central nervous system (CNS). Stressful stimuli induce the neuroendocrine response of the hypothalamic-pituitary-adrenal axis, as well as the synthesis of the neurosteroid allopregnanolone (AL) in the brain. This study tested the hypothesis that centrally administered AL could affect the expression of certain genes involved in reproductive functions at the hypothalamus and pituitary levels, as well as pulsatile gonadotropin secretion in sheep under both natural and stressful conditions. Luteal-phase sheep (n = 24) were subjected to a three-day (day 12-14 of the estrous cycle) series of control or AL (4 × 15 μg/60 μL/30 min, at 30 min intervals) infusions into the third ventricle. Acute stressful stimuli (isolation from other sheep and partial movement restriction) were used in the third day of infusion. Stressful stimuli reduced kisspeptin-1 mRNA levels in both the mediobasal hypothalamus (MBH) and the preoptic area (POA), while pro-dynorphin (PDYN) mRNA level only in the MBH. AL alone decreased the abundances of these transcripts in both structures. Stress increased the expression of gonadotropin-releasing hormone (GnRH) mRNA in the MBH and POA, luteinizing hormone (LH) β subunit (LHβ) mRNA in the anterior pituitary (AP) and pulsatile LH secretion. In contrast, mRNA level of follicle stimulating hormone (FSH) β subunit (FSHβ) was decreased in the AP, with no effect of stress on pulsatile FSH secretion. In stressed sheep, AL counteracted the increase in GnRH mRNA expression only in the POA, but it decreased the level of this transcript in both hypothalamic tissues when infused alone. AL prevented the stress-induced increase in LHβ mRNA expression in the AP and pulsatile LH secretion, as well as inhibited almost all aspects of FSH secretion when administered alone. The suppressive effect of AL on GnRH receptor mRNA expression was also observed in both MBH and AP. We concluded that acute stress and AL exerted multidirectional effects on hypothalamic centers that regulate reproductive functions and secretory activity of AP gonadotrophs in sheep. However, we indicated the dominant inhibitory effect of AL under natural and stressful conditions.

中文翻译：

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别孕酮对自然和应激条件下绵羊中枢生殖功能的影响

生殖功能可能受到整合在中枢神经系统 (CNS) 中的内部和外部因素的影响。压力刺激诱导下丘脑-垂体-肾上腺轴的神经内分泌反应，以及大脑中神经甾体别孕酮 (AL) 的合成。这项研究检验了这样一个假设，即在自然和压力条件下，中央给予 AL 可以影响某些涉及下丘脑和垂体水平生殖功能的基因的表达，以及绵羊的脉动促性腺激素分泌。黄体期绵羊（n = 24）接受为期三天（发情周期的第 12-14 天）系列对照或 AL（4 × 15 μg/60 μL/30 分钟，以 30 分钟间隔）输注到第三脑室。在输注的第三天使用急性压力刺激（与其他绵羊隔离和部分运动限制）。压力刺激降低了中基底下丘脑 (MBH) 和视前区 (POA) 中的 Kisspeptin-1 mRNA 水平，而仅在 MBH 中降低了强啡肽原 (PDYN) mRNA 水平。单独的 AL 降低了两种结构中这些转录本的丰度。压力增加了 MBH 和 POA 中促性腺激素释放激素 (GnRH) mRNA、垂体前叶 (AP) 中促黄体生成素 (LH) β 亚基 (LHβ) mRNA 和搏动性 LH 分泌的表达。相比之下，AP 中促卵泡激素 (FSH) β 亚基 (FSHβ) 的 mRNA 水平降低，压力对 FSH 的脉动分泌没有影响。在应激绵羊中，AL 仅在 POA 中抵消了 GnRH mRNA 表达的增加，但是当单独输注时，它降低了两种下丘脑组织中这种转录物的水平。AL 阻止应激诱导的 AP 中 LHβ mRNA 表达的增加和搏动的 LH 分泌，并在单独给药时抑制 FSH 分泌的几乎所有方面。在 MBH 和 AP 中也观察到 AL 对 GnRH 受体 mRNA 表达的抑制作用。我们得出结论，急性应激和 AL 对调节绵羊 AP 促性腺激素的生殖功能和分泌活动的下丘脑中枢产生多向影响。然而，我们指出了 AL 在自然和压力条件下的主要抑制作用。以及单独给药时几乎抑制 FSH 分泌的所有方面。在 MBH 和 AP 中也观察到 AL 对 GnRH 受体 mRNA 表达的抑制作用。我们得出结论，急性应激和 AL 对调节绵羊 AP 促性腺激素的生殖功能和分泌活动的下丘脑中枢产生多向影响。然而，我们指出了 AL 在自然和压力条件下的主要抑制作用。以及单独给药时几乎抑制 FSH 分泌的所有方面。在 MBH 和 AP 中也观察到 AL 对 GnRH 受体 mRNA 表达的抑制作用。我们得出结论，急性应激和 AL 对调节绵羊 AP 促性腺激素的生殖功能和分泌活动的下丘脑中枢产生多向影响。然而，我们指出了 AL 在自然和压力条件下的主要抑制作用。