The testis is the primary male reproductive organ, tasked with producing sperm and synthesizing male sex hormones. This complex process relies on a coordinated effort between two principal non-germ cell populations: Leydig cells and Sertoli cells. Leydig cells reside in the interstitial spaces, the connective tissue between the seminiferous tubules, while Sertoli cells are located inside the tubules, forming the structural lining. Their functions are intimately linked to maintain reproductive health.
The Endocrine Role of Leydig Cells
Leydig cells are the endocrine factories of the testis, specializing in steroid hormone production through steroidogenesis. They are located within the interstitial compartment, outside the seminiferous tubules where sperm develop. Their primary output is testosterone, an androgen fundamental for male development, maintaining secondary sexual characteristics, and regulating reproductive tissues.
Testosterone synthesis is controlled by the pituitary gland through the release of Luteinizing Hormone (LH). When LH binds to Leydig cell receptors, it initiates a signaling cascade that transports cholesterol into the mitochondria. Cholesterol is the precursor molecule, and its movement into the inner mitochondrial membrane is the rate-limiting step in its conversion to pregnenolone, which is then processed into testosterone within the smooth endoplasmic reticulum.
Hormone production operates within a negative feedback loop to the brain. Testosterone and its byproducts travel to the hypothalamus and pituitary, signaling them to suppress LH secretion, regulating hormone production. The androgens produced by Leydig cells are circulated throughout the body and delivered locally to the seminiferous tubules, where they support sperm development.
The Structural and Supportive Role of Sertoli Cells
Sertoli cells are often referred to as “nurse cells” because they provide the structural and metabolic support necessary for spermatogenesis (sperm production). These elongated cells line the inside of the seminiferous tubules, providing a nurturing environment for developing germ cells. A unique feature of Sertoli cells is their ability to form the Blood-Testis Barrier (BTB).
The BTB is created by tight junctions between adjacent Sertoli cells, dividing the tubule into two compartments. This physical seal isolates the later stages of developing sperm cells from the immune system, preventing an autoimmune response. Sertoli cells also provide direct nourishment to the germ cells, secreting factors like lactate, which serves as a metabolic substrate for the developing sperm.
Sertoli cell function is influenced by Follicle-Stimulating Hormone (FSH), also released from the pituitary gland. FSH binding promotes the synthesis and secretion of proteins, including Androgen Binding Protein (ABP) and inhibin. ABP is secreted into the tubular fluid where it binds to Leydig cell testosterone, maintaining the high local androgen concentrations necessary to drive spermatogenesis. Inhibin, a Sertoli cell product, acts as a negative feedback signal to the pituitary, suppressing FSH secretion.
Essential Differences and Regulatory Partnership
The fundamental difference between the two cell types lies in their location and primary output. Leydig cells occupy the interstitial space and function as the primary hormonal source, secreting steroid hormones like testosterone into the bloodstream. Conversely, Sertoli cells are situated within the seminiferous tubules, functioning as structural and metabolic support cells directed toward maintaining the internal tubular environment.
Their regulatory controls also differ; Leydig cells respond predominantly to Luteinizing Hormone (LH), while Sertoli cells are primarily responsive to Follicle-Stimulating Hormone (FSH). Despite these differences, the cells are engaged in an obligate regulatory partnership, communicating through paracrine factors. Testosterone, the main Leydig cell product, must diffuse into the seminiferous tubule to bind to Sertoli cell-produced ABP, making the androgen essential for successful sperm development.
Sertoli cells, in turn, secrete factors that influence Leydig cell function. Conditioned medium from Sertoli cells enhances the steroidogenic activity of Leydig cells, indicating a positive feedback mechanism that promotes testosterone production. This bidirectional communication ensures that the two main testicular functions, steroidogenesis and spermatogenesis, are tightly synchronized.