Template:Short description Template:Infobox cell Leydig cells, also known as interstitial cells of the testes and interstitial cells of Leydig, are found adjacent to the seminiferous tubules in the testicle and produce testosterone in the presence of luteinizing hormone (LH).<ref name="Chabner">Template:Cite book</ref><ref name="Johnson">Template:Cite book</ref> They are polyhedral in shape and have a large, prominent nucleus, an eosinophilic cytoplasm, and numerous lipid-filled vesicles.<ref name="Zhou">Template:Cite book</ref> Males have two types of leydig cells that appear in two distinct stages of development: the fetal type and the adult type.<ref name="OLC">Template:Cite journal</ref>
StructureEdit
The mammalian Leydig cell is a polyhedral epithelioid cell with a single eccentrically located ovoid nucleus. The nucleus contains one to three prominent nucleoli and large amounts of dark-staining peripheral heterochromatin. The acidophilic cytoplasm usually contains numerous membrane-bound lipid droplets and large amounts of smooth endoplasmic reticulum (SER).<ref name="Rhoades">Template:Cite book</ref> Besides the abundance of SER with scattered patches of rough endoplasmic reticulum, several mitochondria are also prominent within the cytoplasm. Reinke crystals have lipofuscin pigment and rod-shaped crystal-like structures 3 to 20 micrometres in diameter.<ref name="Partin">Template:Cite book</ref>
Life cycleEdit
Fetal-type Leydig cells are present from the 8th to the 20th week of gestation, 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 luteinizing hormone (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.<ref name="pmid20190545">Template:Cite journal</ref>
Adult-type Leydig cells differentiate in the postnatal testis and are dormant until puberty.<ref name="Nieschlag">Template:Cite book</ref> 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.<ref>Template:Cite journal</ref>
Androgen productionEdit
Leydig cells release a class of hormones called androgens (19-carbon steroids).<ref name=":0" /> They secrete testosterone, androstenedione and dehydroepiandrosterone (DHEA), when stimulated by the luteinizing hormone (LH), which is released from the anterior pituitary in response to gonadotropin releasing hormone which in turn is released by the hypothalamus.<ref name=":0" />
LH binds to its receptor (LHCGR) which is a G-protein coupled receptor and consequently increases the production of cAMP.<ref name=":0" /> cAMP, in turn through protein kinase A activation, stimulates cholesterol translocation from intracellular sources (primarily the plasma membrane and intracellular stores) to the mitochondria, firstly to the outer mitochondrial membrane and then cholesterol needs to be translocated to the inner mitochondrial membrane by steroidogenic acute regulatory protein, which is the rate-limiting step in steroid biosynthesis. This is followed by pregnenolone 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.<ref name=":0">Template:Cite journal</ref>
In rats, prolactin (PRL) increases the response of Leydig cells to LH by increasing the number of LH receptors expressed on Leydig cells.<ref name="Steinbach">Template:Cite book</ref>
Clinical significanceEdit
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.<ref name="Partin"/> 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.<ref name="Agha">Template:Cite journal</ref><ref name="Reinke1">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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.<ref name="Jameson">Template:Cite book</ref> A Leydig cell tumour in a child usually causes precocious puberty.<ref name="Jameson"/> About 10% of boys with the tumour have gynecomastia.<ref name="Jameson"/> Although a Leydig cell tumour is always benign in children, it is malignant in 10% to 15% of adults.<ref name="Jameson"/> It is the most common testicular cancer of non-germ cell origin.<ref name="Henningsen">Template:Cite book</ref>
Sonography may be used to identify cystic areas, but it is unable to tell benign tumours apart from malignant tumours.<ref name="Henningsen"/>
Adrenomyeloneuropathy is another example of a disease affecting the Leydig cell.<ref name="Chovel-Sella">Template:Cite book</ref> In this case, a person's testosterone may fall despite higher-than-normal levels of LH and follicle-stimulating hormone (FSH).
In the ovaryEdit
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 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.<ref name="OLC"/> They seem to differentiate from neural crest cells.<ref>Template:Cite journal</ref>
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.<ref>{{#invoke:citation/CS1|citation
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- 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.<ref>Template:Cite journal</ref>
- Leydig cell hyperplasia, where there are only microscopic aggregates of OLC.<ref>{{#invoke:citation/CS1|citation
|CitationClass=web }}</ref>
EtymologyEdit
Leydig cells are named after the German anatomist Franz Leydig, who discovered them in 1850.<ref>Template:WhoNamedIt</ref>
Additional imagesEdit
- Gray1114.png
Section of a genital cord of the testis of a human embryo 3.5 cm long
- Leydig cell tumour2.jpg
Intermediate magnification micrograph of a Leydig cell tumour, H&E stain
- Leydig cell tumour3.jpg
High magnification micrograph of a Leydig cell tumour, H&E stain
- Leydig cells.JPG
Cross-section of seminiferous tubules; arrows indicate location of Leydig cells
See alsoEdit
ReferencesEdit
External linksEdit
Template:Male reproductive system {{#invoke:Navbox|navbox}} Template:Authority control