Estrogens function

Bellacosa, A., Testa, J.R., Staal, S.P., Tsichdis, P.N. A role for akt in mediating the estrogenic functions of epidermal growth factor and insulin-like growth factor. Science 1991, 254, 274-277. 

Hormone defects at key point in the hormonal pathways may give rise to a variety of syndromes in which there are increased or decreased mineralocorticoid, glucocorticoid and/or androgen-estrogen function. 

Fig. 1. Estrogen and estrogen mimics. Many natural plant compounds (e.g. coumestrol) and synthetic chemicals (e.g. ethynylestradiol, diethylstilbestrol, 4-nonylphenol, o,p DDT, and kepone) act as endocrine disruptors by mimicking or blocking normal estrogen function via estrogen receptor dependent or independent mechanisms.

Testosterone is a steroid. It is found in all mammals and is secreted by the testes in the male and the ovaries in the female. Estrogens function as the primary female sex hormones, although they are also present in males in lower levels. They both are derived from cholesterol through various intermediates (Figure 4.16). 

Steroidal and Nonsteroidal Estrogens. Modification of the basic steroid skeleton and the nature of the functional groups in the B, C, and D rings while maintaining the phenoHc A-ring has continued to be a primary approach in the development of new estrogens with unique biological profiles. 

Estrogens coordinate the systemic response during the ovulatory cycle, including the growth and maintenance of the reproductive tract, pituitary, breasts, and other tissues. Estrogens are also responsible for maturation of the skeleton and development of female secondary sex characteristics when females enter puberty. The other important functions of estrogens include modulation of many metaboHc processes (76). 

Steroid Hormones and Neurosteroids. Steroids (qv) can affect neuroendocrine function, stress responses, and behavioral sexual dimorphism (78,79) (see Steroids). Mineralocorticoid, glucocorticoid, androgen, estrogen, and progesterone receptors are localized in the brain and spinal cord. In addition to genomic actions, the neurosteroid can act more acutely to modulate the actions of other receptors or ion channels (80). Pregnenolone [145-13-17, ( ) dehydroepiandosterone [53-43-0] C H2 02 (319) are excitatory neurosteroids found in rat brain, independent of adrenal... 

Xenobiotic induced disruption of female fertility follows essentially the same pattern as that of the male and can be caused by changes in pituitary-hypothalamic function, primary disruption of ovarian structure or hormone secretion, or changes in the rate of hormone deactivation. In addition, there may be changes in the synthesis of estrogen induced production of the yolk protein by the liver (vitellogenesis), which in turn can lead to failure to lay down sufficient yolk in the developing oocytes. Vitellogenesis provides a valuable biomarker for endocrine dysfunction in both sexes,but is more properly considered as part of the liver function. 

Female sexual development and behaviour in mammals occurs by default and requires no ovarian secretion, and it is only in genetic males that the testis can secrete hormones which destroy this female pattern and superimpose that of the male. Sexual differentiation is not so well defined in fish, and larval exposure to both synthetic estrogens and androgens is widely used in aquaculture to produce monosex cultures. Endocrine disruption of sexual differentiation in fish may therefore reflect both the complexity and diversity of such processes between different species. Some care is required in use of the terms hermaphrodite and sex-reversal since a true hermaphrodite has both functional testes and ovaries and a sex-reversed fish is fully functional as its final sex—both produce the appropriate viable gametes. Such functional sex-reversal is not possible in mammals, but in some species of fish it is the normal developmental pattern. In most of the cases of hermaphroditism or sex-reversal reported in the non-scientific press, there is evidence only for a few ovarian follicles within a functional testis. This may be considered as feminisation or a form of intersex, and is very clearly endocrine disruption, but it is certainly neither sex-reversal nor hermaphroditism. In some cases the terms have even been used to infer induction of a single female characteristic such as production of yolk-protein by males. 

The liver plays an important role in the endocrine system. The concentrations of hormones in plasma, and the activity of the glands which secrete them, are determined by the rate at which they are deactivated by the liver. The liver also has a major function in female reproduction since it is the target tissue of ovarian estrogen, to which it responds by producing the yolk protein vitellogenin. " Xenobiotics that affect either of these functions can therefore be considered to be potential endocrine disrupters. 

Therapeutic Function Estrogen used in hormone therapy for prostate cancer Chemical Name 4,4 -(1,2-Diethyl-1,1-ethenediyl)bisphenol-bis(dihydrogen phosphate) Common Name Fosfestrol Structural Formula ... 

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