Leydig cell

ERa 6q25.1 595 aa 17(3-Estradiol (E2) AGGTCA Ovary, uterus, mammary gland, vagina, testis (Leydig cells), bone... 

ER B 14q22-q24 530 aa, 583 aa, further isoforms 17p-Estradiol (E2) AGGTCA Ovary, testis (Sertoli and Leydig cells, efferent ducts), prostate, bone, thymus, spleen, brain... 

Testiculat androgens are synthesized in the interstitial tissue by the Leydig cells. The immediate precursor of the gonadal steroids, as for the adrenal steroids, is cholesterol. The rate-limiting step, as in the adrenal, is delivery of cholesterol to the inner membrane of the mitochondria by the transport protein StAR. Once in the proper location, cholesterol is acted upon by the side chain cleavage enzyme P450scc. The conversion of cholesterol to pregnenolone is identical in adrenal, ovary, and testis. In the latter two tissues, however, the reaction is promoted by LH rather than ACTH. 

In male Sprague-Dawley rats, there was a dose-related increase in testicular Leydig cell tumors and a slight increase in tubular renal adenocarcinoma at the 600-ppm exposure level after exposure for 104 weeks (Maltoni et al. 1986, 1988). EPA and other groups regard such increases as indicative of a hazard potential unless there are reasons to rule this out. However, other authorities believe testicular tumors are common in rats that are not exposed to toxic substances. 

In addition, a recent primate study reported that dietary consumption of soy infant formula reduced the neonatal testosterone surge and increased Leydig cell numbers in the testes of male marmosets. However, the longterm effects on the fertility of the animals has not been determined, and the health implications of these findings for humans are unclear (Sharpe et al,... 

An in vitro study demonstrated decreased testosterone output by Leydig cells with addition of TOCP (Chapin et al. 1990), and suggested that the TOCP metabolite, saligenin cyclic-o-tolyl phosphate, may be the responsible agent for eliciting this effect. 

Chapin RE, Phelps JL, Somkuti SG, et al. 1990. The interaction of sertoli and leydig cells in the testicular toxicity of tri-ort/zo-cresyl phosphate. Toxicol Appl Pharmacol 104 483-495. 

Decreases in sperm motility and increased acid phosphatase activity were reported to result from oral administration of 0.05 mg/kg lead in drinking water to male rats for 20-30 days in a study from the former U.S.S.R. (Krasovskii et al. 1979). Dystrophic changes of the Leydig cells were reported in gonadal tissues of rats exposed to doses as low as 0.005 mg lead/kg/day. The weaknesses of the study include absence of data on the strain and number of rats used, and the fact that PbB levels were not reported. 

LH promotes synthesis of testosterone, the major male androgen (Box 11.5) by the testicular Leydig cells. FSH sensitizes these cells to the activities of LH, probably by increasing LH receptor numbers on the cell surface. Leydig cells have a limited storage capacity for testosterone ( 25 pg), but secrete 5-10 mg of the hormone into the bloodstream daily in young healthy males. 

The androgens and oestrogens represent the major male and female sex hormones respectively (Figure 11.B3). The testicular Leydig cells represent the primary source of androgens in the male, of which testosterone is the major one. Testosterone, in turn, serves as a precursor for two additional steroids, i.e. dihydrotestosterone and the oestrogen called oestradiol. These mediate many of its biological effects. 

Depressed testosterone production of Leydig cells at 20 mg/kg BW and higher normal histology... 

Forgacs, Z., K. Paksky, P. Lazar, and E. Tatrai. 1998. Effect of Ni2+ on the testosterone production of mouse primary Leydig cell culture. Jour. Toxicol. Environ. Health 55A 213-224. 

LH complexes with receptors on the Leydig cell testicular membrane and stimulates the production of testosterone and small amounts of estrogen. 

Permethrin may behave like estrogen in females but antiandrogen in males when administered to immature female and male rats at 10-800 mg/kg [154]. Treatment of rats with permethrin at 10 mg/kg/day during gestation produced fetal death and feminization of male fetuses [155]. Reductions in sperm count and motility and in serum testosterone were noted in a 6-week repeated dose study in mice at 35 mg/kg/day. Permethrin may cause mitochondrial membrane impairment in Leydig cells, resulting in inhibition of testosterone biosynthesis [156]. 

Zhang SY, Ito Y, Yamanoshita O et al (2007) Permethrin may disrupt testosterone biosynthesis via mitochondrial membrane damage of Leydig cells in adult male mouse. Endocrinology 148 3941-3949... 

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