The testes are the male organs responsible for producing sperm and synthesizing sex hormones. This process relies on the coordinated actions of two distinct cell populations: Sertoli cells and Leydig cells. Sertoli cells reside inside the seminiferous tubules, where sperm development occurs. Leydig cells are positioned in the interstitial space just outside these tubules. Together, they regulate male reproductive health and hormonal balance.
Sertoli Cells: The Nurishing and Protective Structure
Sertoli cells, often called “nurse cells,” line the interior of the seminiferous tubules, providing structural and nutritional support for sperm production (spermatogenesis). They surround and guide developing germ cells from spermatogonia to spermatozoa. Sertoli cells also perform phagocytosis, engulfing and digesting cellular debris shed by maturing sperm.
A defining feature is the blood-testis barrier (BTB), formed by tight junctions between adjacent Sertoli cells. This barrier separates developing sperm from the general circulation and the immune system. Since developing sperm are genetically distinct, the BTB prevents an autoimmune attack. The barrier maintains a regulated microenvironment, controlling molecular passage and concentrating testosterone necessary for sperm maturation.
Sertoli cells are active endocrine secretors, producing several regulatory proteins and hormones. They produce Inhibin B, which signals the pituitary gland to suppress Follicle-Stimulating Hormone (FSH) release when sperm production is adequate. During fetal development, Sertoli cells secrete Anti-Müllerian Hormone (AMH), causing the regression of structures that would develop into female reproductive organs. They also produce Androgen-Binding Protein (ABP), which binds testosterone to maintain the high local concentration required for spermatogenesis within the tubules.
Leydig Cells: The Primary Source of Androgens
Leydig cells, or interstitial cells, are located in the connective tissue between the seminiferous tubules, near blood vessels. Their primary function is the synthesis and secretion of androgens, mainly testosterone. Testosterone is released into the bloodstream for systemic effects and locally into the testicular tissue.
Testosterone production is controlled by Luteinizing Hormone (LH), released by the anterior pituitary gland. LH binds to Leydig cell receptors, initiating a signaling cascade that stimulates steroid hormone biosynthesis. Cholesterol is converted into testosterone, which is then secreted.
Testosterone serves a dual purpose. Systemically, it drives the development of male secondary sex characteristics, including muscle mass and bone density. Locally, the high concentration of testosterone diffuses to the neighboring Sertoli cells, where it is required to maintain spermatogenesis.
Intercellular Communication and Hormonal Regulation
The functions of the Sertoli and Leydig cells are integrated into a sophisticated system known as the Hypothalamic-Pituitary-Gonadal (HPG) axis. The hypothalamus releases Gonadotropin-Releasing Hormone (GnRH), which stimulates the pituitary gland to release the two gonadotropins: Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH).
LH targets Leydig cells to stimulate testosterone production, while FSH targets Sertoli cells to regulate their supportive functions for spermatogenesis. The testicular cell products then provide feedback to the central control centers. Testosterone travels through the bloodstream and suppresses the release of LH and GnRH from the pituitary and hypothalamus, preventing overproduction.
Sertoli cells release Inhibin B in response to the rate of spermatogenesis. Inhibin B acts specifically on the pituitary gland to reduce FSH secretion. Local cross-talk also occurs within the testis: Leydig cell testosterone must bind to receptors on Sertoli cells to be effective. Additionally, Sertoli cells secrete factors that can modulate Leydig cell function and testosterone secretion.
Consequences of Sertoli and Leydig Cell Dysfunction
Disruption of these cell types primarily impacts fertility and hormonal status. Sertoli cell dysfunction often causes infertility due to failure in supporting germ cells, resulting in impaired sperm production. Sertoli Cell-Only Syndrome (SCOS) is a severe condition characterized by the complete absence of germ cells within the tubules, leading to non-obstructive azoospermia (lack of sperm in the ejaculate).
Leydig cell failure causes hypogonadism, characterized by insufficient testosterone production. Deficiency symptoms include fatigue, reduced libido, and decreased muscle and bone density. The body attempts to compensate for low testosterone by elevating pituitary LH and sometimes FSH levels, known as compensated Leydig cell dysfunction.
Both cell types can be the origin of specific testicular tumors, though they are rare. Leydig cell tumors (LCTs) often secrete hormones, causing endocrine anomalies like precocious puberty in children or gynecomastia in adults. Sertoli cell tumors are less common but may also be hormonally active. Understanding the cell of origin is crucial for diagnosis and treatment.