Role of sex hormones in the modulation of cholangiocyte function

Figure 1 Two-pathway theory of estrogen-receptor-dependent growth. Many estrogen target cells contain growth-stimulatory and -inhibitory pathways. Both pathways are mediated through ERs. Tamoxifen may possess relatively high affinity for the growth-inhibitory pathway whereas estrogen can mainly activate the growth-stimulatory pathway. However, any ligand for ER can stimulate both pathways.

Figure 2 Scheme of the two classes of hormones, steroids and peptide hormones that successively can be divided in corticoids and sex hormones.

Figure 3 The biosynthesis of the sex hormones starts with the oxidation of the side chain of cholesterol, which is catalyzed by the enzyme cytochrome P450_scc to form pregnenolone. The next steps in the biosynthesis of testosterone can proceed via two different routes. Pregnenolone can be oxidised first by cytochrome P450_17a to 17a-hydroxypregnenolone. The enzyme 3β-HSD also can convert pregnenolone first into progesterone. Both pregnenolone and progesterone are accepted as substrate by the enzyme cytochrome P450_17a. In this way, after 3β-hydroxy-5-androstene-17-one (DHEA) synthesis, there is the testosterone and successively the estradiol formation.

Figure 4 Scheme of hypothalamic-pituitary-gonadal (HPG) axis control exerted by both circulating and in situ locally produced estradiol in men. This axis controls development, reproduction, and aging in animals. The hypothalamus produces gonadotropin-releasing hormone (GnRH). The pituitary gland produces luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and the gonads produce estrogen, progesterone and testosterone from different kinds of cells.

Figure 5 Some representative immunohistochemistry for Erα, progesterone and prolactin receptors in normal and bile duct ligation (BDL) rats. A, B: Erα receptors; C, D: progesterone receptors; E, F: prolactin receptors. The expression of all these receptors is highly increased after BDL compared with that in the biliary epithelium of the normal animal. Original magnification × 40.

Figure 6 Immunohistochemistry for ERα, progesterone and prolactin receptors in liver sections from patients affected with polycystic liver disease. A: Erα receptors; B: progesterone recepors; C: prolactin receptors. Also in course of human cholangiopathies, these three considered receptors seem to play an important role in cholangiocyte physiology. Original magnification × 20.