Leydig cells: What are they? Morphology, Function, Development and Testosterone Replacement Therapy

They are also called the interstitial cells of the testes and are responsible for producing androgens, such as testosterone.

This is the male sex hormone responsible for the growth and maintenance of germ epithelial cells and the development of secondary sexual characteristics.

Leydig cell morphology

The leydig cell has a rounded, irregular polyhedral, and occasionally elongated shape, and is approximately 20 microns in diameter.

They are located in the testes (in the parenchyma of the testicular gonads), they form groups in the angular spaces between the interstitium of the testes near the seminiferous tubules and are usually associated with blood vessels.

The nucleus of the leydig cell is central and low in heterochromatin , with one or two prominent nucleoli.

The cytoplasm is acidophilic and very abundant, containing many long mitochondria with tubular ridges attached to the rough endoplasmic reticulum.

The most abundant cytoplasmic organelle is the smooth endoplasmic reticulum.

Leydig cells often show Reinke’s cytoplasmic crystals, clustered in the cytoplasm. The function of these crystals is unknown.

It has a large Golgi complex, centrioles, lipid droplets and abundant lipochromic pigment granules.

Leydig cells do not have secretory vesicles, so it is thought that testosterone is released with the same speed with which it is synthesized.


The Leydig cells secrete testosterone, after puberty, which is the most important sex hormone in men.

The production of luteinizing hormone is controlled by a stimulus that sends the pituitary through the bloodstream.

Luteinic hormone develops the number and function of Leydig cells.

By binding to its membrane receptor on Leydig cells, it will cause an increase in the concentration of cyclic adenosine monophosphate.

Cyclic adenosine monophosphate is a nucleotide that acts as a messenger in various biological processes in the cytoplasm .

As a consequence, the expression of genes to proteins occurs, these are enzymes that catalyze reactions from cholesterol to testosterone.

The steroidogenic acute regulatory protein acts in this complex to enhance the movement of cholesterol across membranes and thus increase testosterone formation.

Testosterone is the hormone that determines male characteristics such as: the differentiation of male genitalia and cerebral masculinization, it also regulates male reproductive function.

These cells are believed to be the cause of some forms of infertility.

Decreased testosterone production occurs in many young and aging men, resulting in quality-of-life and metabolic changes.


Interstitial cells (Leydig) probably originate from the mesonephros and develop outside the testicular cord, in the testes.

From the seventh week they secrete increasing amounts of testosterone.

The maximum is reached in the course of the second trimester, when the final differentiation in the direction of the male phenotype takes place.

During the development of the fetal testis, fetal Leydig cells originate from multiple progenitor cells.

The specification and function of fetal Leydig cells are under strict regulation of specific genes and signaling proteins.

The Sértoli cells are located inside the seminiferous tubules, and surround the germ cells, forming the blood-testicular barrier.

The functions of Sértoli cells are the phagocytosis of cellular debris produced during the differentiation of germ cells, for the correct proliferation and differentiation of primitive spermatogonia.

It is important to note that the synthesis of the specific receptor protein for androgen in supporting cells (Sertoli) is encoded by a gene on the X chromosome.

A mutation in this gene is responsible for the insusceptibility to androgens (feminizing testes).

In the target organ, testosterone diffuses through the cell membrane where it binds to cytoplasmic receptor proteins and is therefore transported to the cell nucleus in this way.

Within the nucleus of the cell it binds to a nuclear receptor and this hormone-receptor complex is finally able to bind to regions of DNA, which regulates the transcription of a number of additional proteins.

Depending on the type of target organ involved, testosterone is active (Wolff mesonephric duct, epididymis, seminal vesicle, among others) or functions as a precursor hormone and is only activated with its transformation through endohydotestosterone 5-reductase (external genital organs, urogenital sinus).

In addition to its role in embryonic development, testosterone is also important for the expression of secondary characteristics of the male sex.

The main function of fetal Leydig cells is to produce androgens to masculinize male embryos.

Testosterone replacement therapy

One of the main functions of Leydig cells is to produce testosterone after stimulation by the pituitary luteinizing hormone.

Leydig cells, through the synthesis of testosterone, play a key role in sex determination by inducing differentiation of Wolffian ducts in male reproductive organs.

In addition, the Leydig cells produce an insulin-like growth factor that is required for scrotal descent of the testis.

Cultured Leydig cells are a useful in vitro model to better understand testicular development and to develop treatments for male reproductive disorders.

Testosterone replacement therapy is widely used to raise serum testosterone levels in hypogonadal men.

With the acquired knowledge of the mechanisms involved in the formation of testosterone, it is also conceivable to use pharmacological means to increase serum testosterone by stimulation with Leydig cells.