Corpéchot C, Young J, Calvel M, Wehrey C, Veltz J N, Touyer G, Mouren M, Prasad V V, Banner C, Sjövall J
Lab Hormones, INSERM U33, Le Kremlin-Bicêtre, France.
Endocrinology. 1993 Sep;133(3):1003-9. doi: 10.1210/endo.133.3.8365352.
A RIA procedure for measuring progesterone (PROG), 5 alpha-pregnane-3,20-dione (5 alpha-DH PROG), and 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-TH PROG) has been developed and validated by GLC/mass spectrometry. Measurements were made in intact and adrenalectomized (ADX) male rats, in cyclic, pregnant, spayed, and spayed-ADX females, and in both males and spayed females injected with PROG. The predominant contribution of the ovary to the concentrations of 3 alpha,5 alpha-TH PROG in plasma and brain, was indicated by its larger levels in females, in particular during pregnancy, and by its presence in ovarian tissue and disappearance after ovariectomy. An additional adrenal origin in both males and females was shown. Neither PROG nor 5 alpha-DH PROG disappeared from brain, contrary to plasma, after combined adrenalectomy and gonadectomy, thus suggesting that PROG might be synthetized de novo in brain. However, the concentrations of 3 alpha,5 alpha-TH PROG in plasma and brain of female rats were positively correlated with the concentrations of PROG in plasma, indicating that plasma PROG was the major precursor of 3 alpha,5 alpha-TH PROG. The direct formation of 3 alpha,5 alpha-TH PROG from PROG in brain was strongly suggested by the increased 3 alpha,5 alpha-TH PROG/PROG ratios in brain vs. plasma, when measured in control females, and after injection of PROG to both males and OVX females. It was previously reported that 3 alpha,5 alpha-TH PROG is a sedative/anxiolytic steroid, as a result of its binding to gamma-aminobutyric acid (GABA)A receptors and allosteric potentiation of GABAcergic neurotransmission. Its concentrations in brain reach indeed the neuroactive range in cyclic and pregnant females, and are compatible with a physiological role of this neurosteroid.
已开发出一种用于测量孕酮（PROG）、5α-孕烷-3,20-二酮（5α-DH PROG）和3α-羟基-5α-孕烷-20-酮（3α,5α-TH PROG）的放射免疫分析程序，并通过气相色谱/质谱法进行了验证。对完整和肾上腺切除（ADX）的雄性大鼠、处于发情周期、怀孕、绝育以及绝育-肾上腺切除的雌性大鼠，以及注射了PROG的雄性和绝育雌性大鼠进行了测量。卵巢对血浆和大脑中3α,5α-TH PROG浓度的主要贡献表现为，雌性大鼠中该物质水平更高，尤其是在怀孕期间，且卵巢组织中存在该物质，卵巢切除后其消失。结果表明，雄性和雌性大鼠中还存在肾上腺来源。与血浆不同，在联合肾上腺切除和性腺切除后，PROG和5α-DH PROG并未从大脑中消失，因此提示PROG可能在大脑中从头合成。然而，雌性大鼠血浆和大脑中3α,5α-TH PROG的浓度与血浆中PROG的浓度呈正相关，表明血浆PROG是3α,5α-TH PROG的主要前体。当在对照雌性大鼠中以及向雄性和去卵巢雌性大鼠注射PROG后进行测量时，大脑中3α,5α-TH PROG/PROG比值相对于血浆升高，这有力地提示了大脑中PROG可直接形成3α,5α-TH PROG。此前有报道称，3α,5α-TH PROG是一种镇静/抗焦虑类固醇，因为它与γ-氨基丁酸（GABA）A受体结合并对GABA能神经传递产生变构增强作用。在发情周期和怀孕的雌性大鼠中，其在大脑中的浓度确实达到了神经活性范围，这与这种神经甾体的生理作用相符。
