Anti-hormone Therapy

22 J. Hoffmann · A. Sommer
Most targets for the endocrine therapy are components of the hypothalamo–pituitary–gonadal/adrenal
axis (Fig. 1). Interference with this finely
tuned endocrine feedback loop can inhibit both, the hormone biosynthesis
and the binding of endogenous hormones to steroid hormone receptors. The
interference with the gonadotropin-releasing hormones (GnRH) inhibits the
secretion of luteinising hormone (LH), follicle-stimulating hormone (FSH) or
adrenocorticotropic hormone (ACTH) resulting in a decreased synthesis of
the steroid hormones estrogen, progestin and androgen in the testes, ovaries
or adrenal glands [1–4]. The estrogen, progesterone and androgen receptors
(ER, PR, AR), which are activated by estrogens, progestins and androgens, respectively,
are the downstream targets in endocrine-responsive tissues or in
tumours. Historically, agonistic ligands are called hormones and antagonistic
ligands are called anti-hormones.
Enzymes that are involved in steroid hormone biosynthesis or in steroid
metabolism are also targets of anti-hormonal therapy. Recently, it was discovered
that certain co-factors modulate the signalling of steroid hormone
receptors in a tissue-selective fashion. By binding the receptor ligand complex,
these co-activators and co-repressors are capable of either activating or
repressing transcription, respectively [5].
Fig. 1 Endocrine feedback cycle