Biological Effects of Estrogens

The dimerization of ER can involve either homo- or heterodimers—(ER-a)2, (ER-/8)2, or ER-a/ ER-y8—thus expanding the physiological specificity and action of estrogen in the target tissue. Breast tumors that contain ER are treated with selective estrogen response modifiers (SERMs). Current assays for ER in breast tumors only identify ER-a, but ER-a- negative, ER- 8- positive tumors may also respond to SERM therapy. 

Myometrium Estrogen decreases the resting membrane potential of the myometrium and increases ciliary activity of the endometrial epithelium. Rising levels of estradiol prior to ovulation cause the smooth muscle of the fallopian tubes to become increasingly contractile at about the time of ovulation. This and the increased activity of cilia on the endometrial lining facilitate entry of the oocyte-cumulus complex into the lumen of the fallopian tube at the time of ovulation. In the pregnant uterus shortly before parturition, estradiol stimulates the formation of gap junctions and the production of myometrial receptors for oxytocin, PGF, and PGE, and thereby promotes the myometrial contractions that facilitate parturition. 

Estrogen inhibits osteoclast-mediated resorption of cancellous and cortical bone by a direct effect on the osteoclasts and 

Estrogen inhibits the bone-mobilizing effect of parathyroid hormone (PTH) by a direct effect on the osteoblasts (Chapter 37). 

Skin Estrogen inhibits the stimulatory effect of androgen (DHT) on pilosebaceous activity, and thereby reduces 

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For Instance, phenobarbital enhances the hydroxylation of warfarin, which is probably responsible for the decreased anticoagulant action of warfarin in man given phenobarbital . Phenobarbital also reduces the biological effectiveness of estrogen by inducing its metabolism . Phenobarbital has also been suggested as a therapeutic agent in the treatment of syndromes associated with overproduction of ovarian ste-roids . 

If the RANKL/OPG system is a final effector on the biology of osteoclasts, then this system should be the basis for the antiresorptive effects of estrogen. Indeed, estrogen stimulates OPG synthesis for osteoblastic cells (Hofbauer et al. 1999), estrogen deficiency induced by OVX results in a decrease in OPG and increased RANKL production, an action that is prevented by estradiol administration, and OPG administration prevents bone loss induced by OVX (Simonet et al. 1997 Hofbauer et al. 2000 Hofbauer 1999). In addition, estrogen can suppress RANKL and M-CSF-induced differentiation of myelomonocytic precursors into multinucleated TRAP+ osteoclasts through an ER-dependent mechanism that does not require mediation by stromal cells (Shevde et al. 2000). Finally, treatment with estradiol inhibits the response of osteoclast precursors to the action of RANKL (Srivastava et al. 2001). 

DubeG, Salas E, Kurtz W, Christie R, Radomsfci M. Effects of estrogen and an estrogen receptor modulator on atherogenesisinnlibits role of NO. biology of nitric oxide Part 6. Eds. Moncada, S., To H, Maeda, H.,... 

There has been considerable interest in characterizing the biological effects of NP and related alkyl-phenols, ever since some were reported to exhibit estrogenic activity. Structure-activity studies with al-kylphenols have shown clearly that the branching pattern, length of carbon chain, and substitution patterns on the phenolic ring have dramatic effects on the biological activity. 

The biological effects of testosterone can be considered by the receptor it activates and by the tissues in which its effects occur at various stages of life. Testosterone can act as an androgen either directly, by binding to the AR, or indirectly by conversion to dihydrotestosterone, Testosterone also can converted to estradiol, which activates the estrogen receptor (Figure 58 ). 

Lundh, T. (1990b). Uptake, metabohsm and biological effects of plant estrogens in sheep and cattle. Report no. 195. Sveriges lantbruksuniversitet, Institutionen for Husdjurens Utfodring och Yard,... 

Vethaak, A.D., Lahr, J., and Schrap, S.M. et al. (2005). An integrated assessment of estrogenic contamination and biological effects in the aquatic environment of the Netherlands. 

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