In this article we will discuss about Testosterone. After reading this article you will learn about: 1. Meaning of Testosterone 2. Source of Testosterone 3. Synthesis 4. Transport 5. Catabolism 6. Control of Secretion.
Meaning of Testosterone:
Testosterone is primary male sex hormone and popularly known as male androgen. David and his colleagues (1935) isolated pure crystalline hormone from testicular material and named it “Testosterone”. The chemical structure of testicular androgenic principle was elucidated and synthesized by Ruzicka and Wettstein in 1935.
Testosterone is C19 steroid and its chemical formula is C19H28O2. In normal male, 4- 12 mg of testosterone are secreted each day.
Source of Testosterone:
Testosterone is secreted by leydig cells of testis. Trace amount is also secreted by Sertoli cells of seminiferous tubule and adrenal cortex.
Synthesis of Testosterone:
Cholesterol is the precursor for the synthesis of testosterone. Cytochrome P450 side chain cleavage enzyme of the inner mitochondrial membrane of leydig cells hydroxylates the side chain C22 and C20 of cholesterol and converts into pregnenolone. It is then trans-located to smooth ER for conversion to testosterone in two pathways (1) ∆5 pathway and (2) ∆4 pathway. The conversion of pregnenolone to testosterone requires the action of 5-enzymes—(i) 3β-hydroxysteroid dehydrogenase (3β-OHSD). (ii) ∆5-4 isomerase, (iii) 1 7α-hydroxylase, (iv) C17 20 Lyase and (v) 1 7β-hydroxy steroid dehydrogenase (1 7β- OHSD).
1. ∆5 pathway/Dehydroepiandrosterone pathway:
Pregnenolone is changed to dehydroepiandrosterone (DHEA) through 1 7α-hydroxypregnenolone by the actions of microsomal 1 7α-hydroxy- lase and C17 20 Lyase. DHEA is then converted to testosterone either through ∆5 androsterone in presence of enzyme 1 7β-OHSD, 3β-OHSD and ∆5-4 isomerase or through androstenedione with the help of enzymes, 3β-OHSD, ∆5-4 isomerase and 1 7β-OHSD.
2. ∆4 pathway/progesterone pathway:
Most of the pregnenolone is converted to progesterone in presence of enzymes, 3β-OHSD and ∆5,4 isomerase in human. Progesterone is then converted to androstenedione through 17α-hydroxyprogesterone with the help of enzymes 1 7α- hydroxylase and 1 7, 20 Lyase. Androstenedione is finally converted to testosterone by the action of 1 7β-OHSD.
Testosterone is the primary active hormone, however, in many tissues, testosterone is metabolised into dihydrotestosterone (DHT) in presence of enzyme 5α- reductase. This conversion mostly occurs in peripheral tissues. Sometimes in liver testosterone is converted to 1 7-ketosteroids (Fig. 6.10).
Transport of Testosterone:
Plasma proteins mainly help in transport of testosterone. Of the total production about 40% is bound to P-globulin called sex hormone-binding globulin (SHBG) or testosterone-estrogen binding globulin (TEBG) and 40% is bound to albumin and 17 % to other proteins. Only trace amount (2-3%) is unbound in peripheral blood. Before enter into target cell, the protein is dislodged and the hormone binds to specific receptor.
Catabolism of Testosterone:
Testosterones are mainly catabolized in the liver to 1 7-ketosteroids like androsterone, etiocholanolone and are excreted through urine as glucuronides and sulfate conjugates.
Control of Secretion:
The secretion of testosterone from leydig cells is predominantly regulated by ICSH (LH) adenohypophysis. Pituitary hormone secretion is controlled by ICSH-RH of hypothalamus. Thus hypothalamohypophysial system controls the testosterone secretion. High blood titre of testosterone inhibits both pituitary gonadotrophs and hypothalamic releasing hormone by negative feedback mechanism (Fig. 6.11).
Stress, emotion and high fever may reduce the testosterone secretion.