Origin, Development and Regulation of Human Leydig Cells (original) (raw)
Related papers
Hormonal Control of Leydig Cell Differentiationa
Annals of the New York Academy of Sciences, 1991
Identity of Leydig Cell Progenitors Recent studies provide clues regarding the identity of Leydig cell progenitors. In the rat, a small number of Leydig cells (fewer than 200,000 per testis) develop in the fetus and are present at These fetal Leydig cells are not progenitors of the adult Leydig cells because they atrophy and do not divide postnatally. Therefore, adult
Morphological and functional maturation of Leydig cells: from rodent models to primates
Human reproduction update, 2015
Leydig cells (LC) are the sites of testicular androgen production. Development of LC occurs in the testes of most mammalian species as two distinct growth phases, i.e. as fetal and pubertal/adult populations. In primates there are indications of a third neonatal growth phase. LC androgen production begins in embryonic life and is crucial for the intrauterine masculinization of the male fetal genital tract and brain, and continues until birth after which it rapidly declines. A short post-natal phase of LC activity in primates (including human) termed 'mini-puberty' precedes the period of juvenile quiescence. The adult population of LC evolves, depending on species, in mid- to late-prepuberty upon reawakening of the hypothalamic-pituitary-testicular axis, and these cells are responsible for testicular androgen production in adult life, which continues with a slight gradual decline until senescence. This review is an updated comparative analysis of the functional and morphologi...
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2018
The insulin family of growth factors (insulin, IGF1, and IGF2) are critical in sex determination, adrenal differentiation, and testicular function. Notably, the IGF system has been reported to mediate the proliferation of steroidogenic cells. However, the precise role and contribution of the membrane receptors mediating those effects, namely, insulin receptor (INSR) and type-I insulin-like growth factor receptor (IGF1R), have not, to our knowledge, been investigated. We show here that specific deletion of both Insr and Igf1r in steroidogenic cells in mice leads to severe alterations of adrenocortical and testicular development. Double-mutant mice display drastic size reduction of both adrenocortex and testes, with impaired corticosterone, testosterone, and sperm production. Detailed developmental analysis of the testes revealed that fetal Leydig cell (LC) function is normal, but there is a failure of adult LC maturation and steroidogenic function associated with accumulation of prog...
Fetal Leydig Cells Persist as an Androgen-independent Subpopulation in the Postnatal Testis
Molecular endocrinology (Baltimore, Md.), 2015
Two distinct types of Leydig cells emerge during the development of eutherian mammals. Fetal Leydig cells (FLCs) appear shortly after gonadal sex differentiation, and play a crucial role in masculinization of male fetuses. Meanwhile, adult Leydig cells (ALCs) emerge after birth and induce the secondary male-specific sexual maturation by producing testosterone. Previous histological studies suggested that FLCs regress completely soon after birth. Furthermore, gene disruption studies indicated that androgen signaling is dispensable for FLC differentiation, but indispensable for postnatal ALC differentiation. Here, we performed lineage tracing of FLCs using a fetal Leydig cell enhancer of the Ad4BP/SF-1 (Nr5a1) gene, and found that FLCs persist in the adult testis. Given that postnatal FLCs expressed androgen receptor (AR) as well as luteinizing hormone (LH) receptor (LuR), the effects of AR disruption on FLCs and ALCs were analyzed by crossing AR knockout (ARKO) mice with FLC-specific...
Endocrinology, 2005
It is established that androgens and unidentified Sertoli cell (SC)-derived factors can influence the development of adult Leydig cells (LC) in rodents, but the mechanisms are unclear. We evaluated adult LC development and function in SC-selective androgen receptor (AR) knockout (SCARKO) and complete AR knockout (ARKO) mice. In controls, LC number increased 26-fold and LC size increased by approximately 2-fold between 12 and 140 d of age. LC number in SCARKOs was normal on d 12, but was reduced by more than 40% at later ages, although LC were larger and contained more lipid droplets and mitochondria than control LC by adulthood. ARKO LC number was reduced by up to 83% at all ages compared with controls, and LC size did not increase beyond d 12. Serum LH and testosterone levels and seminal vesicle weights were comparable in adult SCARKOs and controls, whereas LH levels were elevated 8-fold in ARKOs, although testosterone levels appeared normal. Immunohistochemistry and quantitative PCR for LC-specific markers indicated steroidogenic function per LC was probably increased in SCARKOs and reduced in ARKOs. In SCARKOs, insulin-like factor-3 and estrogen sulfotransferase (EST) mRNA expression were unchanged and increased 3-fold, respectively, compared with controls, whereas the expression of both was reduced more than 90% in ARKOs. Changes in EST expression, coupled with reduced platelet-derived growth factor-A expression, are potential causes of altered LC number and function in SCARKOs. These results show that loss of androgen action on SC has major consequences for LC development, and this could be mediated indirectly via platelet-derived growth factor-A and/or estrogens/EST.
Biology of Reproduction, 1992
Mature Leydig cells, the main source of testicular testosterone in mammals, arise from immature mesenchymal precursors through an LH-dependent differentiation process. In order to study the steroidogenic potential of these precursors, undifferentiated mesenchymal cells were obtained from the testicular interstitium of two patients with androgen insensitivity syndrome. After double digestion with collagenase and separation of the suspensions in a Percoll density gradient, the cells were cultured in Ham's F12 medium: Dulbecco's Modified Eagle Medium (1:1) supplemented with antibiotics, transferrin, insulin, hydrocortisone, and vitamin E with or without I LU of hCG/ml. At 11 days in culture, samples were removed for morphological characterization and determination of 3-hydroxysteroid dehydrogenase activity (3-HSD). Testosterone concentration was determined by MA in the culture medium at different intervals. Cultured cells were mesenchymal in appearance, elongated in shape, with numerous processes running in different directions. No mature Leydig cells were present. In basal conditions, the percentages of 3-HSD-positive cells at 11 days on patients 1 and 2 were 33% and 28%, respectively, and the testosterone concentrations in the culture media were 4.8 and 8.4 ng 106 cells 24 h, respectively. In cultures stimulated with hCG, there was an increase of histochemical reactivity (47% and 42% in patients 1 and 2, respectively) and in the amount of testosterone secreted (10.2 and 12.0 ng 106 cells, respectively). Electron microscopic studies of cultures grown in the absence of hCG demonstrated a homogenous population of poorly differentiated, fibroblastic-type mesenchymal cells. Cultures stimulated with hCG for 11 days showed a marked increase in organelles, particularly the number of mitochondria and smooth endoplasmic reticulum cisternae, which adopted a pattern resembling the one classically associated with steroid secretion. We report here a successful culture of human testicular mesenchymal cells, demonstrating that immature Leydig precursors are capable of testosterone synthesis and secretion and should, therefore, be included in the family of testosterone-producing cells. Addition of hCG increases testosterone secretion and promotes a trophic effect, triggering early cytologic differentiation toward mature Leydig cells. We are greatly indebted to Clara Cullen for her expert laboratory work Thanks are due to Oscar Croxato, MD, and the FundaciOn OftalmolOgica ArgentinaJ. Malbran for the use of the Electron Microscope Facility. The technical help of Yolanth Castafto and Oscar Rodriguez and the secretarial assistance of Maria E. Mones are gratefully acknowledged.