Raeside James I
Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada.
Yale J Biol Med. 2017 Sep 25;90(3):449-461. eCollection 2017 Sep.
The role of steroids in human medicine is well recognized, but the major contributions made by the large domestic animals as a source of material in the discovery, isolation, and determination of the structure of the steroid hormones is less well appreciated. After a brief reminder of the early efforts to obtain a reliable source of steroids for clinical use, the narrative here is to outline one example where success was ultimately achieved for estrogen replacement therapy. Whereas knowledge of the high concentrations of estrogens in urine of pregnant women and mares dates from the late 1920s, it was not until the 1940s that the latter was shown to be a practical source. Initially, the placenta was held to be responsible, but the involvement of the fetus in each case was eventually established. The remarkable enlargement of the human fetal adrenal glands and the fetal gonads in the horse, with characteristic features of steroid secreting tissues, suggested their participation. Ultimately, it was 16-hydroxylation by the fetal liver that resulted in estriol being the major estrogen type, by far, in late human pregnancy. In the mare, the pattern of estrogen production reflected that of the growth and later regression of the fetal gonads. The characteristic production ring-B, unsaturated estrogens in the mare is derived from an alternative pathway involving retention of the additional double bond in the biosynthesis of equilin.
类固醇在人类医学中的作用已得到广泛认可，但大型家畜作为类固醇激素发现、分离和结构测定的物质来源所做出的主要贡献却鲜为人知。在简要回顾了早期为获得可靠的临床用类固醇来源所做的努力之后，本文将概述一个最终在雌激素替代疗法方面取得成功的例子。虽然早在20世纪20年代末就已知道孕妇和母马尿液中含有高浓度的雌激素，但直到20世纪40年代才证明母马尿液是一种实用的来源。最初，人们认为胎盘是产生雌激素的原因，但最终确定在每种情况下胎儿都参与其中。人类胎儿肾上腺和马胎儿性腺的显著增大，具有类固醇分泌组织的特征，表明它们参与了雌激素的产生。最终发现，在人类妊娠后期，胎儿肝脏的16-羟化作用使得雌三醇成为迄今为止主要的雌激素类型。在母马中，雌激素的产生模式反映了胎儿性腺的生长及随后的退化情况。母马中特征性的B环不饱和雌激素的产生源自一条替代途径，该途径涉及在马萘雌酮生物合成过程中额外双键的保留。
