Leydig cells, also known as interstitial cells of the testes and interstitial cells of Leydig, are found adjacent to the

seminiferous tubules Seminiferous tubules are located within the testicles, and are the specific location of meiosis, and the subsequent creation of male gametes, namely spermatozoa. Structure The epithelium of the tubule consists of a type of sustentacular cells ...

in the

testicle A testicle or testis ( testes) is the gonad in all male bilaterians, including humans, and is Homology (biology), homologous to the ovary in females. Its primary functions are the production of sperm and the secretion of Androgen, androgens, p ...

and produce

testosterone Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...

in the presence of

luteinizing hormone Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (G ...

(LH). They are polyhedral in shape and have a large, prominent nucleus, an eosinophilic

cytoplasm The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...

, and numerous lipid-filled vesicles. Males have two types of leydig cells that appear in two distinct stages of development: the fetal type and the adult type.

Structure

The mammalian Leydig cell is a polyhedral epithelioid cell with a single eccentrically located ovoid nucleus. The nucleus contains one to three prominent

nucleoli The nucleolus (; : nucleoli ) is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis. The nucleolus also participates in the formation of signal recognition particles and plays a ro ...

and large amounts of dark-staining peripheral

heterochromatin Heterochromatin is a tightly packed form of DNA or '' condensed DNA'', which comes in multiple varieties. These varieties lie on a continuum between the two extremes of constitutive heterochromatin and facultative heterochromatin. Both play a rol ...

. The acidophilic cytoplasm usually contains numerous membrane-bound lipid droplets and large amounts of smooth endoplasmic reticulum (SER). Besides the abundance of SER with scattered patches of

rough endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for "little n ...

, several

mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

are also prominent within the

. Reinke crystals have

lipofuscin Lipofuscin is the name given to fine yellow-brown pigment Granule (cell biology), granules composed of lipid-containing residues of Lysosome, lysosomal digestion. It is considered to be one of the aging or "wear-and-tear" pigments, found in the l ...

pigment and rod-shaped crystal-like structures 3 to 20 micrometres in diameter.

Life cycle

Fetal-type Leydig cells are present from the 8th to the 20th week of

gestation Gestation is the period of development during the carrying of an embryo, and later fetus, inside viviparous animals (the embryo develops within the parent). It is typical for mammals, but also occurs for some non-mammals. Mammals during pregn ...

, which produce enough testosterone for masculinisation of a male fetus. It's unclear what they differentiate from (as of 2010). Their testosterone-producing precursors are demonstrably present in the 7th week of gestation. Starting from the 8th week, their growth and maintenance are supported by

(LH). Dhh, PGDF-A, PGDF-B, GATA-4, and IGF receptor I may also play a role. They start to regress from the 20th week. Adult-type Leydig cells differentiate in the postnatal testis and are dormant until

puberty Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a female, the testicles i ...

. They originate from Leydig stem cells, which resemble peritubular cells. The stem cells express PGDFRα but not LH receptor or steroidogenic enzymes. Sertoli cells secrete critical factors (LIF, PDGF-α Dhh) to trigger differentiation into progenitor Leydig cells. A combination of growth factors and hormones during puberty (LH, T₃, IGF-1, PDGF-α) trigger the progenitor cells to transition into immature Leydig cells, which are elongated and express high levels of steroidogenic enzymes. These immature cells turn into adult Leydig cells. Once present in a large enough number, the adult Leydig cells do not tend to divide further or be differentiated. Still, at least in mice, a mechanism exists to make more through differentiation when all Leydig cells are killed.

Androgen production

Leydig cells release a class of

hormones A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physiology and behavior. Hormones a ...

called

androgens An androgen (from Greek ''andr-'', the stem of the word meaning ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...

(19-carbon

steroid A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes t ...

s). They secrete

, androstenedione and

dehydroepiandrosterone Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone precursor. It is one of the most abundant circulating steroids in humans. DHEA is produced in the adrenal glands, the gonads, and the brain. It funct ...

(DHEA), when stimulated by the

(LH), which is released from the

anterior pituitary The anterior pituitary (also called the adenohypophysis or pars anterior) is a major Organ (anatomy), organ of the endocrine system. The anterior pituitary is the glandular, Anatomical terms of location#Usage in human anatomy, anterior lobe that t ...

in response to gonadotropin releasing hormone which in turn is released by the

hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...

. LH binds to its receptor ( LHCGR) which is a

G-protein coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large protein family, group of evoluti ...

and consequently increases the production of cAMP. cAMP, in turn through

protein kinase A In cell biology, protein kinase A (PKA) is a family of serine-threonine kinases whose activity is dependent on cellular levels of cyclic AMP (cAMP). PKA is also known as cAMP-dependent protein kinase (). PKA has several functions in the cell, in ...

activation, stimulates cholesterol translocation from intracellular sources (primarily the

plasma membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

and intracellular stores) to the mitochondria, firstly to the outer mitochondrial membrane and then cholesterol needs to be translocated to the

inner mitochondrial membrane The inner mitochondrial membrane (IMM) is the mitochondrial membrane which separates the mitochondrial matrix from the intermembrane space. Structure The structure of the inner mitochondrial membrane is extensively folded and compartmentalized. T ...

by steroidogenic acute regulatory protein, which is the rate-limiting step in steroid biosynthesis. This is followed by

pregnenolone Pregnenolone (P5), or pregn-5-en-3β-ol-20-one, is an endogenous steroid and precursor/metabolic intermediate in the biosynthesis of most of the steroid hormones, including the progestogens, androgens, estrogens, glucocorticoids, and mineraloc ...

formation from the translocated cholesterol via the cholesterol side-chain cleavage enzyme, which is found in the inner mitochondrial membrane, eventually leading to testosterone synthesis and secretion by Leydig cells. In rats,

prolactin Prolactin (PRL), also known as lactotropin and mammotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secr ...

(PRL) increases the response of Leydig cells to LH by increasing the number of LH receptors expressed on Leydig cells.

Clinical significance

Leydig cells may grow uncontrollably and form a Leydig cell tumour. These may be hormonally active, i.e. secrete testosterone. The function of Reinke crystals is unknown, but they appear in the case of Leydig cell tumours. They are found in less than half of all Leydig cell tumors, but when present, they may serve to confirm the diagnosis of a Leydig cell tumor. No other interstitial cell within the testes has a nucleus or cytoplasm with these characteristics, making identification relatively easy. While any age is susceptible to a Leydig cell tumour, Leydig cell tumours are more common in people aged 5 to 10 and 30 to 35. A Leydig cell tumour in a child usually causes precocious puberty. About 10% of boys with the tumour have gynecomastia. Although a Leydig cell tumour is always

benign Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malig ...

in children, it is

malignant Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malig ...

in 10% to 15% of adults. It is the most common

testicular cancer Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle or swelling or pain in the scrotum. Treatment may result in infertility. Risk factors include an c ...

of non-

germ cell A germ cell is any cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate in the primitive streak and migrate via the gut of an embryo to the developing gonads. There, they unde ...

origin.

Sonography Medical ultrasound includes diagnostic techniques (mainly imaging) using ultrasound, as well as therapeutic applications of ultrasound. In diagnosis, it is used to create an image of internal body structures such as tendons, muscles, joints ...

may be used to identify cystic areas, but it is unable to tell benign tumours apart from malignant tumours. Adrenomyeloneuropathy is another example of a disease affecting the Leydig cell. In this case, a person's testosterone may fall despite higher-than-normal levels of LH and

follicle-stimulating hormone Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, puberty, pubertal maturat ...

(FSH).

In the ovary

While Leydig cells are predominantly associated with testosterone production in the male testes, there is a type of ovarian hilus cell found in the

ovaries The ovary () is a gonad in the female reproductive system that produces ova; when released, an ovum travels through the fallopian tube/oviduct into the uterus. There is an ovary on the left and the right side of the body. The ovaries are endocr ...

of adult females. They mainly appear in the hilum of ovary, but can appear elsewhere in the ovary close to blood vessels and nerves. They are very similar to Leydig cells in function (producing testosterone) and morphology, and can arguably be called ovarian Leydig cells (OLCs). Every examine ovary in the 2017 study, healthy or diseased, has identifiable OLCs. They seem to differentiate from neural crest cells. When overgrown the OLCs can cause abnormally high androgen levels. This usually happens after menopause. There are two cases: * Leydig cell tumour, where the cells form a tumor. ** Sertoli–Leydig cell tumour tends to happen in the second or the third decade of a woman's life. It has happened in a younger woman where it was initially mistaken as PCOS or CAH. * Leydig cell hyperplasia, where there are only microscopic aggregates of OLC.

Etymology

Leydig cells are named after the German anatomist Franz Leydig, who discovered them in 1850.

Additional images

File:Gray1114.png, Section of a genital cord of the testis of a human embryo 3.5 cm long File:Leydig cell tumour2.jpg, Intermediate magnification

micrograph A micrograph is an image, captured photographically or digitally, taken through a microscope or similar device to show a magnify, magnified image of an object. This is opposed to a macrograph or photomacrograph, an image which is also taken ...

of a Leydig cell tumour,

H&E stain Hematoxylin and eosin stain ( or haematoxylin and eosin stain or hematoxylin–eosin stain; often abbreviated as H&E stain or HE stain) is one of the principal tissue stains used in histology. It is the most widely used stain in medical diag ...

File:Leydig cell tumour3.jpg, High magnification

of a Leydig cell tumour,

File:Leydig cells.JPG, Cross-section of seminiferous tubules; arrows indicate location of Leydig cells

References

External links

*
Reproductive PhysiologyDiagram at umassmed.edu
{{DEFAULTSORT:Leydig Cell Steroid hormone secreting cells Animal reproductive system Endocrine system anatomy Human cells Scrotum