Androgen regulation of Sertoli cell maturation and function (PhD and Hons)

Summary

Genetic paradigms provide unique opportunity to identify and study the essential androgen-dependent pathways and key molecular targets required for spermatogenesis, which have relevance to potential causes and treatments of male infertility or gonadal tumours, and for advancing new strategies for male contraception.

Supervisor(s)

Dr Charles Allan

Research Location

Concord - ANZAC Research Institute

Program Type

PHD

Synopsis

The gonadotrophins (FSH and LH) and androgens (eg. testosterone) are essential for male reproduction and act upon specific G-protein gonadotrophin (FSH or LH) receptors and the nuclear androgen receptor (AR) respectively to orchestrate maximal testicular function and sperm production. Sertoli cells are crucial and highly specialised testis cells that provide the essential infrastructure and sustenance for sperm development (spermatogenesis). Sertoli cells exclusively express the FSH receptor and are one of the few cells types in the testis to express AR. Our laboratory has developed unique transgenic mouse models to selectively study the roles of FSH and Sertoli cell AR in testicular development and spermatogenesis. A current NHMRC-funded research project continues to create new models to understand to developmental role of AR in the testis, and to explore the strong synergistic effects of combined androgen-FSH activity in the testis. Our genetic paradigms provide unique opportunity to identify and study the essential androgen-dependent pathways and key molecular targets required for spermatogenesis, which have relevance to potential causes and treatments of male infertility or gonadal tumours, and for advancing new strategies for male contraception. Project hypothesis: Coordinated temporal Sertoli cell AR expression (ie. androgen-sensitivity) regulates Sertoli cell differentiation and function, and in combination with FSH regulates key pathways essential for determining ultimate sperm production capacity and fertility. Project aims:

  1. To determine if the AR regulates Sertoli cell differentiation
  2. To determine if the genetic gain of AR activity restores Sertoli cell function and spermatogenesis in adult males after developmentally complete or Sertoli-specific AR loss.
  3. To identify key androgen-regulated genes and pathways in the androgen response with or without FSH.

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Keywords

Infertility & developmental problems, Reproduction & development

Opportunity ID

The opportunity ID for this research opportunity is: 235