Alterations in maternal epidermal growth factor (EGF) effect testicular descent and epididymal development

Cain, Mark P.; Kramer, Stephen A.; Tindall, Donald J.; Husmann, Douglas A.

doi:10.1016/0090-4295(94)90083-3

Cited by 26 publications

(6 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although androgens play a causal role in this process, the hormones likely do not act on the CSL directly, as this tissue does not express detectable levels of AR (Emmen et al, 1998;Hutson et al, 1994). Instead, androgens are believed to act on neighboring cell types (e.g., primordium of the CSL) that release paracrine factors such as epidermal growth factor, which has been shown to ameliorate the effects of flutamide application on descent of the testis (Cain et al, 1994). The concept of paracrine action of steroids during testicular descent and vagina opening may explain why expression of megalin is seen not in the cell types that undergo apoptosis (CSL, vaginal epithelium) but in adjacent tissues such as mesonephric tubules and uterine epithelium (Figures 3C and 6B).…”

Section: Discussionmentioning

confidence: 99%

Role of Endocytosis in Cellular Uptake of Sex Steroids

Hammes

Andreassen

Spoelgen

et al. 2005

Cell

376

288

View full text Add to dashboard Cite

Androgens and estrogens are transported bound to the sex hormone binding globulin (SHBG). SHBG is believed to keep sex steroids inactive and to control the amount of free hormones that enter cells by passive diffusion. Contrary to the free hormone hypothesis, we demonstrate that megalin, an endocytic receptor in reproductive tissues, acts as a pathway for cellular uptake of biologically active androgens and estrogens bound to SHBG. In line with this function, lack of receptor expression in megalin knockout mice results in impaired descent of the testes into the scrotum in males and blockade of vagina opening in females. Both processes are critically dependent on sex-steroid signaling, and similar defects are seen in animals treated with androgen- or estrogen-receptor antagonists. Thus, our findings uncover the existence of endocytic pathways for protein bound androgens and estrogens and their crucial role in development of the reproductive organs.

show abstract

Section: Discussionmentioning

confidence: 99%

Role of Endocytosis in Cellular Uptake of Sex Steroids

Hammes

Andreassen

Spoelgen

et al. 2005

Cell

376

288

View full text Add to dashboard Cite

show abstract

“…Maternal epidermal growth factor partially reversed the adverse effects of the antiandrogen flutamide on the inguinoscrotal descent of the testis in mice, but the mechanism remains unknown (33). Targeted disruption of the Hoxa10 gene in turn caused uni‐ or bilateral cryptorchidism and abnormal development of the gubernaculum, processus vaginalis, inguinal canal and scrotal sac in male mice (27).…”

Section: Descent Of the Testismentioning

confidence: 99%

Development and descent of the testis in relation to cryptorchidism

et al. 2007

View full text Add to dashboard Cite

The testis descends in two phases. Animal studies suggest, that the transabdominal descent of the testis depends on the insulin-like hormone 3 (INSL3). Androgens are important in the inguinoscrotal testicular descent in animals and humans. In general, the cause of cryptorchidism is unknown and the aetiology is possibly multifactorial. Histological changes in cryptorchid testes demonstrate disturbed development.Conclusion: Since testicular descent is regulated by testis-derived hormones, cryptorchidism may reflect a functional defect of the testis. INTRODUCTIONCryptorchidism, i.e. undescended testis, is a common abnormality in newborn boys, and recent prospective studies have described rates of 2-8% among full term boys (reviewed in Ref. 1). Undescended testis is associated with adverse effects on male reproductive health, i.e. a 4-5-fold increased risk of testicular cancer and a risk of infertility (1-3). Here we review current opinions of the fetal and neonatal development of the testis, mechanism of testicular descent, and abnormalities of these processes in cryptorchidism.

show abstract

“…Hutson and his study group have shown a sex dependent masculinization of the genitofemoral nerve which releases calcitonin gene-related peptide (CGRP) into the gubernaculum and causes rhythmic contractions in rodents 15,16 . Cain et al 17 reported that supraphysiologic doses of epidermal growth factor (EGF) can reduce the incidence of antiandrogen-induced (flutamide) cryptorchidism in rats. They also reported that the EGF has no direct effect on Wolffian ducts or the fetal testis.…”

Section: Hormonesmentioning

confidence: 99%

Genetics and Hormones in Testicular Descent

Kaleva¹,

Toppari²

2003

View full text Add to dashboard Cite

Testicular descent is an essential part of normal male sexual development. Any anomaly that disrupts normal testicular descent will be clinically evident as cryptorchidism. Several factors, such as Hoxa-10, epidermal growth factor (EGF), calcitonin gene-related peptide (CGRP), and hormones, especially androgens and insulin-like factor 3 (INSL-3), have been suggested as being regulators of testicular descent. Testicular descent from the lower pole of the kidney into the extraabdominal scrotal sac is a two-stage process of transabdominal and inguino-scrotal migration. The transabdominal phase is androgen independent, whereas the inguinoscrotal phase depends on androgen action. Disruption of androgen action eg. by environmental anti-androgens are suspected as contributing to cryptorchidism. Estrogens can down-regulate INSL-3 production and thereby disturb testicular descent. Familial occurrence in some cases suggests a possible genetic background for cryptorchidism.

show abstract

Alterations in maternal epidermal growth factor (EGF) effect testicular descent and epididymal development

Cited by 26 publications

References 23 publications

Role of Endocytosis in Cellular Uptake of Sex Steroids

Role of Endocytosis in Cellular Uptake of Sex Steroids

Development and descent of the testis in relation to cryptorchidism

Genetics and Hormones in Testicular Descent

Contact Info

Product

Resources

About