Paracrine function of the testicle


A paracrine action is that which is exerted in the nearby cellular environment, as opposed to endocrine which is a system of chemical signals whose action is exerted at a distance in other organs or glands. There is also the intracrine or autocrine action that acts inside the same kind of cell.
In the testicle we can find three types of tissues with different characteristics and of different embryonic origin: interstitial, tubular and tunic.
In the interstitial tissue there are Leydig cells, macrophages and also blood and lymphatic vessels. Leydig cells are derived from mesenchymal cells. They are located outside the seminiferous tubules, respond to the stimulation of LH and are involved in the synthesis of androgens, and are under the paracrine action of growth factors such as IGF-1 (insulin like grow factor). Leyding cells are testosterone-producing cells (between the seminiferous tubules) and this has a paracrine action on Sertoli cells.
In the tubular zone are the seminiferous tubules, in which the Sertoli cells are located. These cells come from the celomic epithelium. They are arranged by enveloping the germinal cells (spermatogonies, spermatocytes and spermatids) during their development, being intimately linked to the sperm maturation process. They respond to FSH by producing androgen binding protein (ABP) and inhibin and are subject to the paracrine action of cytokines and stem cell factor (SCF).
In the tunics there are myoid cells, these cells are surrounding the seminiferous tubules. They perform a rhythmic contraction that causes peristaltic waves that help mobilize sperm and testicular fluids through the seminiferous tubules. This contractile activity is stimulated by oxytocin, serotonin and prostaglandins.
Also, these cells are involved in mediating the effects of hormones and growth factors on sertoli cells and germ cells.

-Other Hormones or Neurotransmitters

Different neurotransmitters and neuropeptides that exert their effects on the central nervous system, serotonin (5-HT) and catecholamines, have also been identified in peripheral tissues such as the testicle.
An inhibitory role of 5-HT on steroidogenic capacity has been found in the purified Leydig cells of rodents . This effect is mediated through serotonergic receptors by stimulation of the intratesticular corticotrophin releasing factor (CRF) system. As far as catecholamines are concerned, it has been shown that, via specific adrenergic receptors, they stimulate the function of the Leydig and Sertoli cells.
Therefore, it has been demonstrated that the adrenergic regulation on the steroidogenic capacity in the testicle is influenced by a local serotonergic system, and this interaction between the catecholaminergic and serotonergic testicular systems implies a specialized regulation on the production of androgens and the existence of a system of signals common to both pathways or a crossed dialogue between them.
Oxytocin and vasopressin are the only known hormones released by the posterior pituitary gland in humans that act at a distance. However, oxytocin neurons make other peptides, including corticotropin-releasing hormone (CRH) and dynorphin, for example, which act locally. The magnocellular neurons that make oxytocin are adjacent to the magnocellular neurons that synthesize vasopressin and are similar in many ways.
After recognition of synthesis sites and projections outside the classical hypothalamus-neurohypophysial system, oxytocin has been implicated in multiple biological processes at the central and peripheral levels. The recognition of the synthesis of oxytocin within the testicle and that contractile structures of the male genital tract contract to oxytocin, suggests a physiological role at this level, which may be related to the modulation of the activity of contractile structures related to sperm transport.
The regulatory mechanisms of prostaglandin synthesis in the testicle show that there are local factors involved in the modulation of cyclooxygenase 2 expression in Leydig and Sertoli cells, a key enzyme for its synthesis from arachidonic acid.
Studies have established: the participation of pituitary hormones (LH, FSH and PRL) and androgens (testosterone, DHT) in the regulation of the expression of cyclooxygenase 2 and the synthesis of prostaglandins in primary cultures of Leydig and Sertoli cells and the stimulating role played by interleukin 1beta on the production of prostaglandins in the testicle of patients suffering from idiopathic infertility. Thus, prostaglandins would play a key role in the regulation of testicular activity in physiological situations, as well as during the development and/or maintenance of certain gonadal dysfunctions that lead to altered spermatogenesis in the human testicle.


The essential function that Sertoli cells exert on the maintenance of germ cells is related, among other aspects, to the fact that these cells provide structural support, create a selective permeability barrier, participate in the movement of germ cells and provide nutrients and regulatory factors to developing germ cells.
Selective permeability barrier: The hemato-testicular barrier is formed at puberty and contributes directly to the complex structural organization of the testicle as it makes possible the creation of a specialized microenvironment that is necessary for germ cell development.
The latter ensures that the body’s immune system does not recognize antigens present on the surface of haploid germ cells. The hemato-testicular barrier is comparable in permeability to the hemato-encephalic barrier. However, it has particular characteristics since the hemato-testicular barrier, unlike the hemato-encephalic barrier, must be opened periodically to allow the passage of sperm cells.
As for the factors that regulate these processes of restructuring of the seminiferous tube, it is known that gonadotrophins, cytokines and growth factors are involved. A set of transduction signals activated by these hormones would interact by regulating the disassembly and assembly of new joints.
Movement of germinal cells. Germ cells lack the characteristic architecture of migrating cells such as fibroblasts, therefore the movement of germ cells towards the tubular light that accompanies the differentiation process is actively controlled by Sertoli cells.
Provision of nutrients and regulatory factors. The specialized microenvironment for the development of spermatogenesis is generated by the secretion by the Sertoli cell of a large amount of substances.
The secretory products include: transport proteins such as transferrin and ceruloplasmin that provide divalent ions to germinal cells, proteases and protease inhibitors such as plasminogen activator, catepsin L and cystatin, which participate in the events of maintenance, repair and remodeling of the tube, hormones and growth factors that in addition to influencing proliferation and tissue growth at certain times of life.
They promote processes of cellular differentiation acting in autocrine or paracrine form, through components of the extracellular matrix that contribute to the structural integrity of the seminiferous epithelium such as type IV collagen and laminin and energetic substrates important for the survival of germinal cells such as pyruvate and lactate.
The pituitary gonadotrophins LH and FSH are fundamental in the functional regulation of the Sertoli cell. This regulation is exercised directly (FSH) or indirectly (LH) through the androgens secreted by the Leydig cell.
It has been shown that the Sertoli cell can also be regulated by numerous growth factors, cytokines and other peptides. The vast majority of these peptides are produced locally in the testicle and modulate in autocrine or paracrine form the hormonal effect exerted by FSH and androgens.

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