VARIACIÓN DE LA CONFIABILIDAD POR PRESENCIA DE LA GENERACIÓN DISTRIBUIDA

Sexual Maturation at puberty (different tissues) 'OERI . cell Growth factors Cholestrol SERTOLI . cell > Plasma Wo l l Ti i i n S l u n u l u t i o n

And rostoied lone

T A Testosterone SEM INIFERUS ^ T U B U L E ^ _Receptor

. o

-

Figure L 7: This schematic diagram shows the regulation and transduction o f pituitary and testis hormones. 5a-reductase (5aR2) converts testosterone to dihydro-testosterone. This changes a weak hormone to more potent hormone and is essential fo r many androgen actions. Deficiency o f this enzyme causes defects in blue boxes. In the seminiferous tubules o f the testis Sertoli cells are one o f it's targets.

critical points in the determination of the sexual distinctions are the quantitative divergence in sex hormone concentrations and the differential expression pattern of steroid hormone receptors.

1.3.3.3.1 Estrogen. Circulating estrogens originate by the aromatization of androgen catalysed by cytochrome P450 aromatase. This enzyme is present and active in germ cells of adult mouse and rat testis (Janulis et al., 1996 and 1998) and its deficiency causes spermatogenic impairment. (Robertson et at., 1999).

Estrogen is also produced by the somatic cell component of the testis (Cook B.A, 1996; McLachlan et a l, 1996). Estrogen may even have an essential role for male fertility because male mice lacking the alpha form of the estrogen receptor are infertile (Eddy et at., 1996).

1.3.3.3.2 Progesterone. Progesterone has no known role in testis function. The main action of progesterone in female genital tract before fertilisation is

progesterone-induced acrosome reaction in human sperm to stimulate release of the acrosomal lytic content (Osman et a/.,1989; Baldi et at., 1995&1998). In high concentrations progesterone inhibits the secretion of FSH and LH (review, De Kretser and Phillips, 1998).

1.3.3.4 Gonadal peptides and growth factors as m ediators of

development and functional control of the testis. Growth factors are proteins that bind to receptors (0 protein-coupled receptors) in the surface of target cells, and either stimulate cell division or alter cell fate. The activation process and function of G proteins will be discussed more in chapter IV.

Sertoli cells produce a number of growth factors. In the foetal testis, one is

seminiferous growth factor (SGF), which stimulates somatic cell proliferation and blood vessel production and causes foetal and postnatal testis development (Feig et at., 1980). In the adult, Sertoli cells respond to their own production of SGF by producing sulfated glycoprotein-2 (SGP-2). SGP-2 is the major secretory product

of adult Sertoli cells and acts as a paracrine signal with a classical negative- feedback control and binds to the membranes of spermatozoa.

Another secretion of Sertoli cells are transform ing growth factors P (TGF- P), a superfamily of growth factors, whose receptors are also expressed in the mammalian testis. TGF-6 members regulate a variety of developmental processes including spermatogenesis (review, Massague, 1998).

The Sertoli cells secrete inhibin, one member of the TGF-P family, a peptide hormone that inhibits FSH secretion (by a classical negative-feedback mechanism) and androgen-binding protein (ABP) that helps testosterone bind within the

seminiferous tubule and stimulates Leydig function (Bremner, 1989; Lin et al.,

1989).

Another category of TGF-6 molecules that plays a role in spermatogenesis is the bone morphogenetic protein (BMP) sub-family. At least one member of this sub-family, BMP8b, which is produced within the germ cells themselves, is

essential for spermatogenesis in mice. It is suggested that BMP8 is required for the resumption of male germ-cell proliferation at puberty and the maintenance of the germ cells in the adult (Zhao et a l, 1996).

Sertoli cells secrete other factors that have both negative and positive effects on Leydig cell functions; activin, arginine vasopressin, the cytokine interleukin-1 (IL-1) and tumour necrosis factor (TNF) have negative effects while endothelin is a stimulator of Leydig cell function. It should be noted that the production of these factors by Sertoli cells may depend on the developmental stage of the associated germ cells thereby stimulating Leydig cells along the length of the seminiferous tubule to periodically produce hormones and growth factors appropriate to the developing germ cells in the adjacent tubule (Saez, 1994; Gnessi et al., 1997).

Apart from androgen hormones, Leydig cells produce small amounts of many hormones the majority of which act directly on the cells that secrete them (autocrine factors). The autocrine factors that inhibit steroidogenesis may include angiotensin II, corticotrophin-releasing factor (CRF), arginine vasopressin (AVP), renin, oxytocin, endorphin, and ACTH. The role of most of these agents in the regulation of testicular function remains undetermined, but it has been reported that endorphin

influences Sertoli cell division and inhibin production (review; Gnessi, et a l, 1997). Gnessi et al. have reviewed many proteins and growth factors which are secreted in the testis by either Sertoli cells or Leydig cells.

In summary, signalling mechanisms in spermatogenesis are associated with different pathways containing a variety of growth factors and proteins. They are encoded by different genes and controlled by cascades of transcription factors some of which are discussed in later sections. Many of these gene products such as growth factors and hormones are not only present in testis but also are associated with other pathways in other tissues. Therefore, to identify specific gene expression in a complex tissue like testis it is necessary to compare it to tissues containing similar pathways and signals.

1.3.4 Exocrine products and semen components.

Sperm is not semen. Spermatozoa mature and are stored in the epididymis. Transport of spermatozoa to the epididymis depends on age and sexual activity. During passage of spermatozoa through the epididymis, the sperm develop an increased capacity for progressive motility and also acquire the ability to penetrate the oocyte during fertilization (review, Moore, 1996). This process of sperm maturation in the epididymis is not well understood, but it has been reported in several publications that the epididymis secretes proteins such as specific androgen- dependent protein and glycoproteins that make changes on the surfaces of

spermatozoa. The modifications of sperm membrane are coordinated carefully at different zones of the epididymis and presumably are important in post-ejaculatory survival and function of the spermatozoa (review, Jones, 1998; review, Moore.

1998).

Secretions from the testis, epididymis, bulbourethral glans (Cowper's glands), glands of Littré (periurethral glands), prostate, and seminal vesicles make up the normal seminal fluid. The fluid is released from the glands in a specific sequence during ejaculation. Final composition of semen is 5% from testes and epididymis, 60% from seminal vesicles, 30% from prostate, 5% from bulbourethral glands (Jequier, 2000). Although the seminal vesicles are responsible for the formation of a

coagulum, proteinase secreted by the prostate is responsible for semen liquefaction. Several proteases, including prostate-specific antigen and plasminogen activators, play a role in semen liquefaction.

Part two