Pharmacology and Clinical Use of Sex Steroid Hormone Receptor Modulators

Abstract

Sex steroid receptors are ligand-triggered transcription factors. Oestrogen, progesterone and androgen receptors form, together with the glucocorticoid and mineralocorticoid receptors, a subgroup of the superfamily of nuclear receptors. They share a common mode of action, namely translating a hormone-i.e. a small-molecule signal-from outside to changes in gene expression and cell fate, and thereby represent "natural" pharmacological targets.For pharmacological therapy, these receptors have originally been addressed by hormones and synthetic hormone analogues in order to overcome pathologies related to deficiencies in the natural ligands. Another major use for female sex hormone receptor modulators is oral contraception, i.e. birth control.On the other side, blocking the activity of sex steroid receptors has become an established way to treat hormone-dependent malignancies, such as breast and prostate cancer.In this review, we will discuss how the experience gained from the classical pharmacology of these receptors and their molecular similarities led to new options for the treatment of gender-specific diseases and highlight recent progress in medicinal chemistry of sex hormone-modulating drugs.

ICRAC controls the rapid androgen response in human primary prostate epithelial cells and is altered in prostate cancer

“…Subsequently, these complexes translocate to the nucleus where they trigger gene expression important for many physiological and pathophysiological functions and thus are targets for therapeutic strategies [1-3]. In contrast to the classical pathway where the hormonal effects appear after hours, many cell types display rapid hormone signaling upon steroid hormone stimulation mediated by receptors or ion channels located at the cell surface [4, 5].…”

Menopausal hormone therapy – a course on individuality

“…Вместе с тем на сегодняшний день доказано, что крат ковременная гормональная терапия не позволяет достичь эффективных результатов и особенно обеспечить долго срочную профилактику возрастных изменений [2,3].…”

Vascular effects of aldosterone: Sorting out the receptors and the ligands

“…Many of the effects of aldosterone are adequately explained by the activation of the classical cytoplasmic and/or nuclear MR acting as a transcription factor. Further, some of the rapid effects of aldosterone may be mediated by cytoplasmic MR tethered to the plasma membrane The MR is member of the steroid hormone nuclear receptor subfamily . However, it has long been speculated that some of the effects of aldosterone are mediated by a membrane‐associated non‐MR‐linked pathway .…”

“…hormone nuclear receptor subfamily. 18,19 However, it has long been speculated that some of the effects of aldosterone are mediated by a membrane-associated non-MR-linked pathway. 20 This, in most part, was based on the insensitivity of these effects to inhibition by spironolactone.…”