Why is The Smith Lab investigating the testis?

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Male health and wellbeing are androgen-dependent. Low circulating testosterone concentration is associated with many increasingly prevalent chronic and age-related clinical conditions. Although the cause/consequence relationship to perturbed androgen action is unclear, an approach to improve endogenous androgen production could be through modulating testicular Leydig cell function. The Smith Lab’s goal is to identify factors that support Leydig cell function and retention throughout life.

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What is The Smith Lab doing to achieve this goal?

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The Smith Lab has used the Cre/lox Recombination system to generate mouse models with selective ablation of:

Androgen receptor in the testis…

Through this The Smith Lab has helped to characterise the previously undescribed paracrine-signalling network which acts to support both steroidogenesis and spermatogenesis. 

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“Our identification of differential androgens pathways leads into our ongoing research focusing on deciphering the importance of both classical and backdoor androgen pathways on testis development and function.”

 

Sertoli cells in the testis…

The Smith Lab has demonstrated that Sertoli cells play an essential role in both Leydig cell development and retention throughout adulthood, a completely new paradigm in testis biology. 

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“Developing from these findings The Smith Lab is pursuing the characterisation of Sertoli cell roles with the goal to potentially utilise their properties as biological therapeutics”

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“We are demonstrating the complexity of Sertoli cell regulation on Leydig cell development and function. The Smith Lab is working towards using Sertoli cells as a novel target for endocrine disruption and/or potential therapy to improve androgen profile.”

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How will this investigation help the problem?

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Together, these investigations highlight a body-wide and lifelong role for androgen-signaling in supporting the health and wellbeing in males. Our future focus is now on understanding how androgen production is controlled within the testis and how this influences not only male fertility, but also other important clinical problems such as cardiovascular disease, diabetes, and age-related conditions.

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“The Smith Lab’s work in this field focuses on dissecting the mechanisms that underlie androgen receptor signaling and Sertoli cell functionality through the use of novel transgenic mouse models coupled to a wide variety of cutting edge molecular genetics and endocrinology techniques.”

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