**5.2. 3β-HSD and 17β-HSD deficiency**

The development of the male internal and external genitalia in an XY fetus requires a complex interplay of many critical genes, enzymes and cofactors. In early fetal life, in the bipotential embryo, both Wolffian ducts and Müllerian ducts are present. Testosterone produced by FLCs acts on AR to stabilize the Wolffian ducts whereas MIS causes regression of Müllerian ducts (George et al., 2010). The formation of male external genitalia is induced by T and DHT.

Hydroxysteroid Dehydrogenases – Localization, Function and Regulation in the Testis 277

In Leydig cells, multiple factors regulate 3β-HSD and 17β-HSD function exerting very diverse effect. Nowadays further characterization of physiological and pathological conditions as well as endogenous and exogenous agents that can modify HSDs expression is becoming increasingly necessary. Especially, in light of recent reports indicating an increase in the incidences of developmental and functional disorders of the male reproductive tract. Exploration of the site and possible mechanisms of action of these agents in steroid

This work was financially supported by the Ministry of Science and Higher Education,

Akingbemi, B.T.; Ge, R.; Rosenfeld, C.S.; Newton, L.G.; Hardy, D.O.; Catterall, J.F.; Lubahn, D.B.; Korach, K.S. & Hardy, M.P. (2003) Estrogen receptor-alpha gene deficiency enhances androgen biosynthesis in the mouse Leydig cell. *Endocrinology*, Vol. 144, No. 1,

Almeida, J.; Conley, A.J.; Mathewson, L. & Ball, B.A. (2011) Expression of steroidogenic enzymes during equine testicular development. *Reproduction*, Vol. 141, No. 6, (June

Andersrson, S.; Geissler, W.M.; Patel, S. & Ling, W. (1995) The molecular biology of androgenic 17β-hydroxysteroid dehydrogenases. *Journal of Steroid Biochemistry and* 

Ariyaratne, H.B.S. & Mendis-Handagama, S.M.L.C. (2000) Structural and functional changes in the testis interstitium of Sprague Dawley rats from birth to adulthood. *Biology of* 

Badrinarayanan, S.; Rengarajan, P.; Nithya, P. & Balasubramanian, K. (2006) Corticosterone impairs the mRNA expression and activity of 3beta- and 17beta-hydroxysteroid dehydrogenases in adult rat Leydig cells. *Biochemistry and Cell Biology*, Vol. 84, No. 5,

Baker, P.J.; Sha, J.A.; McBride, M.W.; Peng, L.; Payne, A.H. & O'Shaughnessy, P.J. (1999) Expression of 3β-hydroxysteroid dehydrogenase type I and type VI isoforms in the mouse testis during development. *European Journal of Biochemistry*, Vol. 260, No. 3,

*Molecular Biology*, Vol. 53, No. 1-6, (June, 1995), pp. 37-39, ISSN 0960-0760

*Reproduction*, Vol. 62, No. 3, (March 2000), pp. 680–690, ISSN 1470-1626

biosynthesis is becoming important future research direction.

Małgorzata Kotula-Balak, Anna Hejmej and Barbara Bilińska

(January 2003), pp. 84–93, ISSN 1477-7827

(October 2006), pp. 745–754, ISSN 0829-8211

(March 1999), pp. 911–917, ISSN 0014-2956

2011), pp. 841-878, ISSN 1470-1626

*Department of Endocrinology, Institute of Zoology, Jagiellonian University, Poland* 

**6. Conclusion** 

**Author details** 

**Acknowledgement** 

Grant N N303816640.

**7. References** 

Disruption in androgen production and/or action leads to disorder of sex development (DSD) also known as male pseudohermaphroditism. DSD is defined as a congenital condition in which development of chromosomal, gonadal or anatomical sex is atypical in such individuals (Hughes et al., 2006). 46, XY DSD is an autosomal recessive form of DSD which was first described in 1971 (Saez et al., 1971). Disturbances of androgen production can occur in all steps of T biosynthesis and its conversion into DHT.

Around 40 various mutations have already been described in *HSD3B2* gene. Mutation in this gene results in 3β-HSD II deficiency and decreased T biosynthesis (Payne & Hales, 2004). Severe form of 3β-HSD deficiency named congenital adrenal hyperplasia (CAH) impairs also steroidogenesis in adrenals (Moisan et al., 1999). In male patients, either perineal hypospadias or perineoscrotal hypospadias and ambiguous external genitalia or microphallus have been reported (Simard et al., 2005). Also, in these individuals gynecomastia has been observed as common at puberty. Serum levels of Δ5 steroids are elevated whereas levels of Δ4 steroids are slightly increased. In adulthood, males with 3β-HSD II deficiency can reach normal levels of T due to the peripheral conversion of elevated Δ5 steroids by 3β-HSD I and/or due to testicular stimulation by high LH levels. Most of the patients with mutation in *HSD3B2* gene are raised as males and display male social sex but there are some cases described where such individuals are castrated in childhood and treated as female (Mendonca et al., 2008). Males with 3β-HSD II deficiency share common clinical features with patients deficient for 17β-HSD 3 and 5α-reductase 2.

Deficiency of the 17β-HSD 3 can be caused by either homozygous or compound heterozygous mutations in the *HSD17B3* gene (Geissler et al., 1994). This autosomal recessive disorder manifests in males as undermasculinization characterized by hypoplasticto-normal internal genitalia (epididymis, vas deferens, seminal vesicles, and ejaculatory ducts), but female external genitalia and the absence of a prostate (Boehmer et al., 1999; Lindqvist et al., 2001; Sinnecker et al., 1996; Ulloa-Aguirre et al., 1985).

At the time of puberty, there is a marked increase in plasma LH and, consequently, in testicular secretion of androstenedione. Mendonca et al. (2010) have found that significant amounts of the circulating androstenedione are converted to T in peripheral tissues by an unidentified member of the 17β-HSD family, thereby causing virilization in many of these individuals. To date, 19 mutations in the *HSD17B3* gene have been found. Most of these patients are raised as girls during childhood but starts to display masculine behavior at puberty (Mendonca et al., 2008).
