The seminiferous epithelium is divided into two compartments by tight junctions formed by Sertoli-Sertoli cell occluding junctions (Fig. 44.6). The basal compartment contains spermatogonia and early-stage primary spermatocytes, while the adluminal compartment contains later-stage primary spermatocytes and all subsequent stages of sperm cells. To allow the movement of early primary spermatocytes from the basal to the adluminal compartment, the tight junctions need to be disassembled and reassembled. These tight junctions form the blood-testis barrier, which creates a specialized immunologically safe environment for developing sperm by restricting the movement of substances between blood and germ cells. The Sertoli cell plays a crucial role in controlling the availability of nutrients to germ cells by blocking paracellular diffusion.

Sperm cell viability and development depend on healthy Sertoli cell function. While testosterone produced by peritubular Leydig cells is essential for spermatogenesis, it is the Sertoli cells that express the androgen receptor and respond to testosterone. Similarly, the Sertoli cell expresses the follicle-stimulating hormone (FSH) receptor, not the developing sperm cells, and FSH is required for optimal sperm production. Thus, these hormones indirectly support spermatogenesis by stimulating Sertoli cell function.

Apart from these functions, Sertoli cells also have multiple additional roles. They express the enzyme CYP19, which converts testosterone to estrogen, potentially enhancing spermatogenesis. Sertoli cells produce androgen-binding protein (ABP), maintaining a high androgen level within the adluminal compartment and the lumens of the seminiferous tubules and male reproductive tract. They also produce a significant amount of fluid, which provides a suitable medium for sperm and assists in moving immotile spermatozoa from the seminiferous tubule into the epididymis. Additionally, Sertoli cells perform phagocytosis by engulfing residual bodies shed by spermatozoa during spermiogenesis.

Furthermore, Sertoli cells play an endocrine role. During development, they produce antimüllerian hormone (AMH) to induce the regression of the embryonic müllerian duct, which would otherwise give rise to the female reproductive tract. Inhibin, another hormone produced by Sertoli cells, is a protein hormone that negatively regulates FSH production by feedback inhibition on gonadotropes, helping to maintain FSH levels within a set point.

The Leydig cell is the primary endocrine cell of the testis, located in the peritubular compartment (Fig. 44.7). This compartment also contains various cell types of loose connective tissue and a highly vascular peritubular capillary network. The capillaries provide nutrients to the seminiferous tubules through Sertoli cells and transport testosterone away from the testes to the peripheral circulation. Leydig cells are steroidogenic stromal cells responsible for synthesizing cholesterol and storing it as cholesterol esters. They obtain cholesterol through de novo synthesis and uptake via LDL receptors and HDL receptors (also known as scavenger receptor BI [SR-BI]).
Fig. 44.6 ). These Sertoli-Sertoli cell occluding junctions divide the seminiferous epithelium into a basal compartment containing the spermatogonia and early-stage primary spermatocytes and an adluminal compartment containing later-stage primary spermatocytes and all subsequent stages of sperm cells. As early primary spermatocytes move apically from the basal to the adluminal compartment, the tight junctions need to be disassembled and reassembled. These tight junctions form the physical basis for the blood-testis barrier (see
Fig. 44.6 ), which creates a specialized immunologically safe microenvironment for developing sperm. By blocking paracellular diffusion the tight junctions restrict movement of substances between blood and the developing germ cells through a trans–Sertoli cell transport pathway and in this manner allow the Sertoli cell to control the availability of nutrients to germ cells.
Healthy Sertoli cell function is essential for sperm cell viability and development. In addition, spermatogenesis is absolutely dependent on testosterone produced by peritubular Leydig cells (see
The Leydig Cell ), yet it is the Sertoli cells that express the androgen receptor and respond to testosterone, not the developing sperm cells. Similarly the pituitary hormone follicle-stimulating hormone (FSH) is also required for maximal sperm production, and again it is the Sertoli cell that expresses the FSH receptor, not the developing sperm. Thus these hormones support spermatogenesis indirectly through stimulation of Sertoli cell function.
Sertoli cells have multiple additional functions. They express the enzyme CYP19 (also called aromatase), which converts Leydig cell–derived testosterone to the potent estrogen estradiol-17β (see ). This local production of estrogen may enhance spermatogenesis in humans. Sertoli cells also produce androgen-binding protein (ABP), which maintains a high androgen level within the adluminal compartment, the lumens of the seminiferous tubules, and the proximal part of the male reproductive tract. Sertoli cells also produce a large amount of fluid. This fluid provides an appropriate bathing medium for the sperm and assists in moving the immotile spermatozoa from the seminiferous tubule into the epididymis. Sertoli cells perform an important phagocytic function by engulfing residual bodies, which represent cytoplasm shed by spermatozoa during spermiogenesis.
Finally, the Sertoli cell has an important endocrine role. During development, Sertoli cells produce antimüllerian hormone (AMH; also called müllerian inhibitory substance), which induces regression of the embryonic müllerian duct that is programmed to give rise to the female reproductive tract (discussed later). The Sertoli cells also produce the hormone inhibin. Inhibin is a heterodimer protein hormone related to the transforming growth factor-β family. FSH stimulates inhibin production, which then negatively feeds back on gonadotropes to inhibit FSH production. Thus inhibin keeps FSH levels within a set point.
The peritubular compartment contains the primary endocrine cell of the testis, the Leydig cell (
Fig. 44.7 ). This compartment also contains the common cell types of loose connective tissue and an extremely rich peritubular capillary network that provides nutrients to the seminiferous tubules (by way of Sertoli cells) while conveying testosterone away from the testes to the peripheral circulation.
The Leydig Cell
Leydig cells are steroidogenic stromal cells. These cells synthesize cholesterol de novo, as well as acquire it through low-density lipoprotein (LDL) receptors and high-density lipoprotein (HDL) receptors (also called scavenger receptor BI [SR-BI]), and store cholesterol as cholesterol esters as