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Male Sex Steroid Hormones
- May 15, 2018 -

In males, LH binds to Leydig cells, stimulating production of the principal Leydig cell hormone, testosterone. Testosterone is secreted to the plasma and also carried to Sertoli cells by androgen binding protein (ABP). In Sertoli cells the Δ4 double bond of testosterone is reduced, by the action of steroid 5α-reductase, producing dihydrotestosterone (DHT). Testosterone and DHT are carried in the plasma, and delivered to target tissue, by a specific gonadal-steroid binding globulin (GBG). In a number of target tissues, testosterone can be converted to DHT. Dihydrotestosterone is the most potent of the male steroid hormones, with an activity that is 10 times that of testosterone. Because of its relatively lower potency, testosterone is sometimes considered to be a prohormone.

Humans express three different steroid 5α-reductase genes, SRD5A1, SRD5A2, and SRD5A3 where SRD5A2 is the primary enzyme carrying out the testosterone to DHT conversion. The SRD5A1 gene is located on chromosome 5p15.31 and is composed of 7 exons that generate three alternatively spliced mRNAs encoding three distinct isoforms of the enzyme. The SRD5A2 gene is located on chromosome 2p23.1 and is composed of 10 exons that encode a protein of 254 amino acids. Mutations in the SRD5A2 gene are the cause of a form of male pseudohermaphroditism. The SRD5A3 gene is located on chromosome 4q12 and is composed of 6 exons that encode a protein of 318 amino acids. In addition to DHT formation, the SRD5A3 encoded enzyme (also called polyprenol reductase) is required for the conversion of polyprenol to dolichol which is necessary for the synthesis of N-linked glycoproteins. Mutations in the SRD5A3 gene are associated with the development of a particular form of congenital disorder of glycosylation (CDG) identified as CDG-Iq.

Synthesis of the male sex hormones

Synthesis of the male sex hormones in Leydig cells of the testis. P450ssc (CYP11A1), 3β-DH (HSD3B2), and P450c17 (CYP17A1) are the same enzymes as those needed for adrenal steroid hormone synthesis. 17,20-lyase is the same activity of CYP17A1 described above for adrenal hormone synthesis. Aromatase (also called estrogen synthetase) is CYP19A1. 17-ketoreductase is also called 17β-hydroxysteroid dehydrogenase type 3 (gene symbol HSD17B3). The full name for the primary form of 5α-reductase is 5α-reductase type 2 (gene symbol SRD5A2). Humans express three 5α-reductase genes identified as SRD5A1, SRD5A2, and SRD5A3.

Testosterone is also produced by Sertoli cells but in these cells it is regulated by FSH, again acting through a cAMP- and PKA-regulatory pathway. In addition, FSH stimulates Sertoli cells to secrete androgen-binding protein (ABP), which transports testosterone and DHT from Leydig cells to sites of spermatogenesis. There, testosterone acts to stimulate protein synthesis and sperm development.