Regulation of sperm production. (A) Hormonal control of spermatogenesis in the testis. Spermatogenesis in the testis is under endocrine and paracrine control, which is regulated by the hypothalamus and the pituitary gland also known as hypothalamic-pituitary-gonadal (HPG) axis. The hypothalamus regulates the hormonal activity of the anterior pituitary gland by secreting the tropic gonadotropin-releasing hormone (GnRH). Upon binding of GnRH to the anterior pituitary gland production of luteinizing hormone (LH) and follicle stimulating hormone (FSH) is elevated which upon blood stream transport stimulate testosterone secretion by intestinal Leydig cells and activation of Sertoli cells by FSH. Sertoli cells as cellular part of the tubular unit provide the optimal environment for the developing germ cells. A negative feedback of GnRH production in the hypothalamic neurons and LH/FSH secretion by the pituitary gland is exerted by high testosterone levels in the blood and secretion of the proteohormone inhibin-B by Sertoli cells. Arrow: positive (green) and negative (red) feedback. (B) Schematic drawing of a single seminiferous tubule with different stages of developing germ cells during spermatogenesis. The cross section shows that germ cells of a distinct developmental stage are organized in concentric layers within the tubule: In the most basal cell layer of the tubular unit, the immature spermatogonial stem cells are located, followed by spermatocytes, round spermatids and finally the most mature elongated spermatids which are concentrated in the lumen of the seminiferous tubule. The regulation of spermatogenesis is mainly mediated by surrounding interstitial Leydig cells which produce testosterone. The Sertoli cells within the seminiferous tubules have a nurturing role for the developing germ cell and transduce the action of FSH to the closely associated germ cells. (C) Schematic drawing showing a sagittal section through a whole testis and the overlying epididymis. The testis contains the tightly packed seminiferous tubules where spermatogenesis takes place. The elongated duct presenting the epididymis at the posterior margin of the testis is subdivided into three discrete segments (caput, corpus, cauda), where the luminal fluid of each region is characterized by a unique composition of different constituents, essential for post-testicular sperm maturation.