and maintenance of spermatogenesis in the germinal epithelium within the seminiferous tubules [71]. Some of the earliest functions of the Leydig cell are associated with regulation of the male reproductive organs, the organization of parts of the brain, pituitary secretion of gonadotropins, and accessory sex organ development of the neonate to ensure the appropriate response by these tissues to testicular steroids in the adult male [69]. The dependence of male sex accessory organs on testicular hormones is not restricted to the early fetal period but occurs also during puberty and throughout male adult life [72].
Table 2.1 Primary steroid and peptide hormones synthesized and/or secreted by the bull testis.
| Hormone family | Hormone | Site of synthesis |
|---|---|---|
| Steroid family | ||
| Cholesterol (27 carbons) | Cholesterol22‐hydroxycholesterol20,22,‐dihydroxycholesterol | De novo biosynthesis, fat deposits, or from blood |
| Progestins (21 carbons) | ∆5‐Pregnenolone17α‐Hydroxypregnenolone17α‐HydroxyprogesteroneProgesterone | Leydig cells (mitochondria) |
| Androgens (19 carbons) | Dehydroepiandrosterone∆4‐Androstenedione∆5‐AndrostenediolTestosteroneDihydrostestosterone | Leydig cells (microsomal compartments) |
| Estrogens (18 carbons) | EstroneEstradiol‐17β | Leydig cells |
| Peptide family | ||
| Relaxin‐like peptides | Relaxin/insulin‐like peptide‐3 | Leydig cells |
| Neuropeptides | OxytocinGlial cell‐derived factor | Leydig cellsSeroli cells |
| Cytokine family | ||
| ActivinInhibin | Sertoli cellsSertoli cells | |
| Glycoproteins | ||
| Androgen binding proteinTesticular transferrin | Sertoli cellsSertoli cells |
Cholesterol has been described as an obligatory intermediate in testosterone synthesis [5]. Testosterone is synthesized from a pool of metabolically active cholesterol, which is derived from either de novo biosynthesis of cholesterol, cholesterol esters stored as lipid droplets in the cell cytoplasm, or from blood plasma [68]. The conversion of cholesterol to testosterone involves five main enzymatic steps that include 20,22‐lyase, 3β‐dehydrogenase isomerase, 17α‐hydroxylase, 17,20‐lyase, and 17β‐hydroxysteroid dehydrogenase, and in some species the conversion of androgens to estrogens via the aromatase enzyme system [73]. Conversion of cholesterol to pregnenolone is the initial step in the pathway and is catalyzed by the cholesterol side‐chain cleavage enzyme complex, a three‐step process that takes place in the mitochondria of the cell [45]. Briefly, pregnenolone is formed from cholesterol (C27 sterol) by cleavage of the bond between C20 and C22 catalyzed by the multienzyme complex of the side‐chain cleavage system in the mitochondria, and metabolized in the microsomes by the microsomal enzyme complex 3β‐hydroxysteroid dehydrogenase/isomerase. Pregnenolone is also an obligatory intermediate in Leydig cell steroid synthesis. Van der Mollen and Rommerts [52] have indicated that the conversion of C21 steroids (i.e. pregnenolone) to C19 steroids (testosterone) may occur in the mammalian testis through two biosynthetic pathways. The crucial step in the biosynthesis of pregnenolone to androgens is the cleavage of the two‐carbon side‐chain of 17α‐hydroxyprogesterone or 17α‐hydroxypregnenolone by the 17,21‐lyase enzyme complex [74]. This is regarded as an irreversible reaction producing “weak” androgens (androstenedione and dehydroepiandrosterone, respectively). Through the action of 17β‐hydroxysteroid dehydrogenase, androstenedione is converted to the more potent androgen testosterone, which occurs in the microsomal compartments of the cell. However, testosterone is converted to dihydrotestosterone (DHT) by the 5α‐reductase enzyme system, and is regarded as the more biologically active androgen produced by the testis. A more detailed account of the mechanisms involved in testosterone biosynthesis can be found in the review by Hall [45], but a schematic overview of steroid synthesis in the bovine testis is presented in Figure 2.2.
Figure 2.2 Synthetic pathway of testosterone and conversion to active androgen and estrogen metabolites in the bull testis. Relevant enzyme systems involved in the synthesis are shown; in some instances, the enzyme reactions are reversible. Color code: blue, C27 cholesterol steroid precursors; purple, C21 progestin steroids; green, C19 androgen steroids; red, C18 estrogen steroids.
The unusual abundance of Leydig cells in domestic boars and stallions promoted the hypothesis that this may be related to the fact that both species secrete significant amounts of estrogens [75], but the significance of the vast quantities of estrogens produced by these two species is unexplained. It has been suggested that estrogens act synergistically with testosterone to enhance both secretory activity of accessory sex organs and sexual behavior in boars castrated after puberty [76]. Estrogens are C18 steroids and are formed by the conversion of androgens by the aromatase enzyme system to produce estrone and estradiol from androstenedione and testosterone, respectively. Of interest in the boar are the musk‐smelling Δ16‐androstene steroids (pheromones) that are regarded quantitatively as the most abundant steroids produced by the boar testis and contribute to the familiar “boar taint” of pork [77]. However, there is insufficient evidence to demonstrate that bull testis produces estrogens in the quantities found in the boar and stallion, nor is there evidence that the bull secretes much in the way of the Δ16‐androstene steroids. However, what is now well documented is that testosterone is the most potent androgen produced by Leydig cells in mammalian testes, and the site of action is primarily on seminiferous tubule target cells, thus influencing the reduction division of the spermatogenic cells [78]. Androgens stimulate production of androgen‐binding protein (ABP) by the Sertoli cells [79], and this acts as an intracellular carrier of testosterone and DHT within the Sertoli cells. Testosterone is also the most important determinant of the rate of formation of fructose by the seminal vesicles and of citric acid by the prostate and seminal vesicle glands of the bull, ram, and human [78].
Oxytocin is a nine amino acid neuropeptide hormone normally associated with the hypothalamic–posterior pituitary system and the regulation of parturition and lactation in the female, but has also been shown to have an endocrine and paracrine role in male reproduction [19, 80]. There is evidence reported in the
