Hormonal control of testicular descent and the cause of cryptorchidism

1994 ◽  
Vol 6 (2) ◽  
pp. 151 ◽  
Author(s):  
JM Hutson ◽  
M Baker ◽  
M Terada ◽  
B Zhou ◽  
G Paxton
Keyword(s):  
Undescended Testis ◽  
Good Evidence ◽  
Hormonal Control ◽  
Testicular Descent ◽  
Second Phase ◽  
Rodent Models ◽  
Paper Briefly ◽  
Calcitonin Gene ◽  
Androgen Resistance ◽  
Androgen Levels

This paper briefly reviews the literature on testicular descent and presents new observations from the authors' laboratory which suggest new ways of looking at old problems. There is now good evidence that testicular descent occurs in two morphologically and hormonally distinct phases. Relative 'transabdominal migration' of the testis compared with the ovary occurs at 10-15 weeks of gestation in the human and 'inguinoscrotal' migration occurs at 26-35 weeks of gestation. We have proposed previously that the first phase is controlled by Mullerian inhibiting substance although this remains controversial. The second phase is androgen dependent and is possibly mediated indirectly through the release from the genitofemoral nerve (GFN) of the neuropeptide calcitonin gene-related peptide (CGRP). Recently we have used three different rodent models of undescended testis to determine the involvement of the GNF and/or CGRP. The testicular feminization mouse with complete androgen resistance and the rat exposed prenatally to the antiandrogen flutamide have a deficiency of CGRP in the GFN. In contrast, the mutant trans-scrotal rat which has normal androgen levels has an excess of CGRP in the GFN. All cryptorchidism models, despite their different primary cause, have in common an abnormality of the GNF and/or CGRP which is consistent with the hypothesis that normal testicular descent in the rodent may be mediated by the GFN.

scholarly journals Effect of an anti-androgen on testicular descent and inguinal closure in a marsupial, the tammar wallaby (Macropus eugenii)

Reproduction ◽  
2002 ◽  
pp. 865-874 ◽  
Author(s):  
D Coveney ◽  
G Shaw ◽  
JM Hutson ◽  
MB Renfree
Keyword(s):  
Dorsal Root ◽  
Inguinal Canal ◽  
Prostate Gland ◽  
Tammar Wallaby ◽  
Calcitonin Gene Related Peptide ◽  
Hormonal Control ◽  
Testicular Descent ◽  
Genitofemoral Nerve ◽  
Related Peptide ◽  
Calcitonin Gene

Androgens are essential for testicular descent in eutherian mammals, but little is known about its hormonal control in marsupials. This study reports the effects of daily treatment with the anti-androgen flutamide (10 mg kg(-1)) from day 9 to day 75 after birth on the descent of the testis and inguinal closure in tammar wallabies. By day 75 after birth, the testes of control males had descended and the prostate gland was well developed. The testes of all flutamide-treated males had passed through the inguinal canal and were situated in the base of the scrotum. Three of the nine flutamide-treated males had unilateral inguinal hernias. The size of the inguinal canal, regardless of whether a hernia was present, was significantly wider than that of control males. Development of the prostate gland was significantly inhibited. By day 75 after birth, the phallus was significantly longer in control males than in females, whereas the phallus of flutamide-treated males was similar to that of control females. In flutamide-treated males, the lumbar 1 dorsal root ganglia was feminized and significantly fewer cell bodies expressed calcitonin gene- related peptide. As the anti-androgen treatment resulted in a reduction in the number of calcitonin gene-related peptide-positive cell bodies in the dorsal root ganglion supplying the genitofemoral nerve, the process of inguinal closure in tammar wallabies may be mediated by calcitonin gene-related peptide via the genitofemoral nerve, as indicated in humans. Flutamide treatment inhibited development of the prostate gland and phallus, which are both androgen-dependent structures, but it did not affect the normal descent of the testis, indicating that testicular descent can proceed when the action of androgens is blocked.

scholarly journals Effects of oestrogen treatment on testicular descent, inguinal closure and prostatic development in a male marsupial, Macropus eugenii

Reproduction ◽  
2002 ◽  
pp. 73-83 ◽  
Author(s):  
D Coveney ◽  
G Shaw ◽  
MB Renfree
Keyword(s):  
Inguinal Canal ◽  
Prostate Gland ◽  
Tammar Wallaby ◽  
Hormonal Control ◽  
Testicular Descent ◽  
Oestrogen Treatment ◽  
Model Animal ◽  
Internal Genitalia ◽  
Mullerian Ducts ◽  
Testicular Migration

This study reports the effect of oestrogen treatment on the development of the genital ducts, prostate gland, testicular descent and inguinal canal closure in male tammar wallaby young treated with oestrogen over four time spans during the first 25 days of pouch life (days 0-10, 10-15, 15-25 and 0-25) and sampled at day 50. In control males, the Mullerian ducts had regressed and the Wolffian ducts had developed into the vas deferens and epididymis. The prostate gland had formed epithelial buds extending from the ventral, lateral and posterior walls of the urethra. The testes were in the neck of the scrotum and the gubernaculum and processus vaginalis were present at the base of the scrotum. In most males treated with oestradiol from day 0 to day 25, the testes had failed to descend by day 50. The gubernaculae were long and thin. The retained Mullerian ducts formed a lateral vaginal expansion like that of normal day 50 females. The Wolffian ducts of the males treated on days 0-25 were regressed, but were present in males in the other three treatment groups. The prostate glands were hyperplastic and epithelial budding was highly invasive. Some treated males from the day 10-25 and 0-25 groups had inguinal hernias. These results demonstrate that oestrogen treatment has profound effects on the development of the internal genitalia of a male marsupial, preventing inguinal closure and interfering with testicular descent. Therefore, the tammar wallaby may provide a useful experimental model animal in which to investigate the hormonal control of testicular migration and closure of the inguinal canal.

scholarly journals Association between Testicular Appendix and Undescended Testicle in children: A comparative study

2021 ◽  
Vol 2 (2) ◽  
pp. 10-14
Author(s):  
Kevin Emeka Chukwubuike ◽  
Keyword(s):  
Comparative Study ◽  
Undescended Testis ◽  
Testicular Descent ◽  
Undescended Testicle ◽  
Appendix Testis

The appendix testis may be involved in the normal testicular descent and there are reports of decreased incidence of appendix testis in children with undescended testis. The aim of this study was to evaluate the incidence of appendix testis in children with undescended testis in comparison to the incidence in children with normally descended testis.

Targeting CGRP via receptor antagonism and antibody neutralisation in two distinct rodent models of migraine-like pain

Cephalalgia ◽  
2019 ◽  
Vol 39 (14) ◽  
pp. 1827-1837 ◽  
Author(s):  
Sarah L Christensen ◽  
Steffen Petersen ◽  
David Møbjerg Kristensen ◽  
Jes Olesen ◽  
Gordon Munro
Keyword(s):  
Rat Model ◽  
Time Course ◽  
Calcitonin Gene Related Peptide ◽  
Current Data ◽  
Rodent Models ◽  
Onset Of Action ◽  
Related Peptide ◽  
Pain Pathways ◽  
Calcitonin Gene ◽  
Cutaneous Hypersensitivity

Introduction Rodent disease models can play an indispensable role in drug development. Confirming that translationally-relevant disease mechanisms are engaged in such models is a crucial facet of this process. Accordingly, we have validated the role of calcitonin gene-related peptide signaling in a mouse model of glyceryl trinitrate-provoked migraine-like pain and a spontaneous rat model of migraine-like pain by assessing their pharmacological responsiveness to the small molecule calcitonin gene-related peptide receptor antagonist olcegepant, and the humanised monoclonal calcitonin gene-related peptide antibody ALD405. Methods Cutaneous sensitivity to hind paw, and periorbital mechanical stimulation were used as surrogate markers of activation of relevant pain pathways in each respective model. Separate experiments were performed to identify the time-course of treatment response to olcegepant (1 mg/kg i.p.) and ALD405 (10 mg/kg i.p.). Results Olcegepant and ALD405 significantly alleviated cutaneous mechanical hypersensitivity in both models compared with corresponding control treatments (saline and IgG control antibody respectively). As expected, the duration of anti-nociceptive action obtained with ALD405 was considerably longer than that associated with olcegepant. Surprisingly, in the spontaneous rat model the onset of action of ALD405 occurred within just 4 hours after administration. Discussion The current data clearly show that calcitonin gene-related peptide-mediated signaling is critically involved in the manifestation of cutaneous hypersensitivity in distinct rodent models of migraine-like pain and emphasise their translational relevance. Moreover, the unexpected rapidity of onset observed for ALD405 supports i) a probable site of action outside the blood-brain barrier, and ii) a potential clinical utility of specific monoclonal calcitonin gene-related peptide antibodies in the abortive treatment of migraine.

Systematic Review and Meta-Analysis of treatment of Palpable Undescended Testis

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Hassan Abdel Monem Abdallah ◽  
Mohamed Soliman El-Debeiky ◽  
Amr Abdel Raouf Abdel Nasser
Keyword(s):  
Systematic Review ◽  
Success Rate ◽  
Hormonal Therapy ◽  
Undescended Testis ◽  
Meta Analysis ◽  
Good Evidence ◽  
Preterm Neonates ◽  
Case Control Studies ◽  
Retrospective Case ◽  
Delay Of Treatment

Abstract Background Undescended testis is the most common endocrinological disease in the male newborn period. Incidence varies between 1.0% and 4.6% in full-term neonates, with rates as high as 45% in preterm neonates. Failure or delay of treatment can result in reduced fertility and/or increased testicular cancer risk in adulthood. Aim and objectives : To establish, through the available literature, which is the best technique, either hormonal therapy or surgical orchiopexy for treatment of palpable undescended testis through systematic review and meta-analysis. Subjects and methods : The review considered case-control studies, case report studies, and retrospective case follow-up evaluating the effectiveness or efficacy of a certain technique of treatment of palpable undescended testicles over other techniques either hormonal therapy and surgical orchiopexy according to age of the patient, This review considered all studies that involve infants with palpable undescended testicles, Search strategy is designed to include both manual and electronic data available. Electronic searches involved searching databases of PubMed (from Jan. 1987 till July 2017), EMbase, CINAHL and Cochrane database. Results The overall success rate of primary orchiopexy is 96.4% and the overall success rate for 2- stage FS is 86%. Conclusion There is good evidence for early placement of undescended testes in the scrotal position to prevent potential impairment of fertility and reduce the risk of testicular malignancy.

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