Frye Cheryl A, Rhodes Madeline E, Raol YogendraSinh H, Brooks-Kayal Amy R
Department of Psychology, University at Albany, Albany, NY 12222, and Division of Neurology, The Children's Hospital of Philadelphia, PA, USA.
Psychopharmacology (Berl). 2006 Jun;186(3):343-50. doi: 10.1007/s00213-005-0253-7. Epub 2006 Feb 21.
The progesterone metabolite 5alpha-pregnane-3alpha-ol-20-one (3alpha,5alpha-THP) is an important modulator of the hypothalamic-pituitary-adrenal axis and stress-induced corticosterone response. Typically, 3alpha,5alpha-THP levels are increased in response to acute stress, which may then reduce corticosterone release from the adrenals. Early postnatal stimulation is a developmental stressor that can produce pervasive endocrine effects.
The present studies investigated the effects of early postnatal stimulation on plasma progestin and corticosterone levels and hippocampal progestin levels of rats.
On postnatal days 9 and 10, rats were either left in their home cage undisturbed or injected intraperitoneally as a means of early stimulation (ES). Tissues were collected on either postnatal day 10 (6 h after last handling experience) or adulthood. Plasma corticosterone, progesterone, and 3alpha,5alpha-THP and hippocampal progesterone and 3alpha,5alpha-THP were measured by radioimmunoassay.
On postnatal day 10, plasma, but not hippocampal, levels of progesterone and 3alpha,5alpha-THP were significantly lower among rats exposed to ES than control rats. These effects occurred concomitant with a tendency for plasma corticosterone to be higher among ES compared to control rats. In adulthood, hippocampal 3alpha,5alpha-THP was significantly lower among ES vs control rats.
Together, these data suggest that ES may influence immediate secretion of 3alpha,5alpha-THP and corticosterone and have pervasive effects in adulthood on the biosynthesis and/or metabolism of progestins in the hippocampus.
孕酮代谢产物5α-孕烷-3α-醇-20-酮(3α,5α-四氢孕酮)是下丘脑-垂体-肾上腺轴以及应激诱导的皮质酮反应的重要调节因子。通常情况下,急性应激会使3α,5α-四氢孕酮水平升高,进而可能减少肾上腺皮质酮的释放。出生后早期刺激是一种发育应激源,可产生广泛的内分泌影响。
本研究探讨出生后早期刺激对大鼠血浆孕激素和皮质酮水平以及海马体孕激素水平的影响。
在出生后第9天和第10天,将大鼠留在其饲养笼中不受干扰,或通过腹腔注射作为早期刺激(ES)的手段。在出生后第10天(最后一次处理后6小时)或成年期收集组织。通过放射免疫分析法测定血浆皮质酮、孕酮和3α,5α-四氢孕酮以及海马体孕酮和3α,5α-四氢孕酮。
在出生后第10天,接受早期刺激的大鼠血浆中的孕酮和3α,5α-四氢孕酮水平显著低于对照大鼠,但海马体中的水平无显著差异。这些影响伴随着与对照大鼠相比,早期刺激组大鼠血浆皮质酮水平升高的趋势。在成年期,早期刺激组大鼠海马体中的3α,5α-四氢孕酮水平显著低于对照大鼠。
这些数据共同表明,早期刺激可能影响3α,5α-四氢孕酮和皮质酮的即时分泌,并在成年期对海马体中孕激素的生物合成和/或代谢产生广泛影响。