Hormones, mimics steroid

Chi, D.Y., O Neil, J.P., Anderson, C.J., Welch, M.J. and Katzenellen-bogen, J.A. (1994) Homodimeric and heterodimeric bis(amino thiol) oxometal complexes with rhenium(V) and technetium(V). Control of heterodimeric complex formation and an approach to metal complexes that mimic steroid hormones. J. Med. Chem. 37 928-937. 

Compounds that mimic the effects of sex steroids in some tissues, while at the same time can oppose endogenous hormone action in other tissues. 

In Australia, lambing in sheep has dropped to as little as 30% after grazing on subterranean clover. Trifolium subterraneum. The clover contains the isoflavonoids formononetin and genistein (Fig. 11.11). These compounds mimic the steroidal nucleus of the natural female hormone estrone. Alfalfa, M. sativa, and ladino clover. Trifolium repens, contain the even more potent isoflavonoid coumestrol. It is 30 times more active than genistein or formononetin, but occurs in lower concentrations in the plant (Shutt, 1976). 

Terpenoids are structurally based on the isoprenoid (C5) unit and include monoterpenoids, sesquiterpenoids, diterpenoids, triterpenoids, steroids and carotenoids. These compounds can be further modified to generate greater structural complexity. Thus the saponins are surface active amphiphiles deriving from the glycosylation of steroid (C27) or triterpenoid (C30) entities. Plant triterpenoids with very specific biochemical effects include those that mimic the effects of mammalian steroid hormones or of insect developmental hormones. 

The excessive production of thyroid hormone in Graves disease is associated with an enlarged thyroid gland, but in this case a circulating immunoglobulin that mimics the activity of thyroid stimulating hormone (TSH) is implicated. Finally, we saw in an earlier section how an inappropriate steroid hormone may be secreted in excessive amounts when specific enzymes in the adrenal steroid biosynthetic pathway are present at inadequate levels. 

Xenobiotics can adversely affect the normal functions of the cells/organs of the reproductive system. These agents may induce a variety of outcomes, including prevention of ovulation and impairment of ovum transport, fertilization, or implantation. Endocrine disruptors may mimic endogenous hormones as well as directly destroy cellular components, leading to cell death. More indirect effects may include inhibition of key enzymes involved in steroid synthesis. 

Human chorionic gonadotropin stimulates production of gonadal steroid hormones. The interstitial and corpus luteal cells of the female produce progesterone, and the Leydig cells of the male produce testosterone. hCG can be used to mimic a midcycle LH surge and trigger ovulation in a hypogonadotropic woman. 

The health effect of endocrine disruptors is further complicated by the fact that an endocrine disrupter or a family of endocrine disruptors may have multiple mechanisms of actions. For example, PCBs may mimic estrogen, prevent binding of thyroid hormone to thyroid binding globulin, and accelerate the metabolism and excretion of several steroid hormones. 

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