Andrology Laboratory
Professor David Handelsman
The Andrology Laboratory is primarily focused on the study of male reproductive biology. Principle areas of research include male fertility and the hormonal regulation of sperm production (spermatogenesis) and testicular development. Current investigations use unique transgenic mouse models to study the role of follicle-stimulating hormone (FSH) in spermatogenesis, the actions of testosterone and the androgen receptor (AR) in gonadal maturation and function, as well as the controversial role of estrogens in the testis. The research projects listed below provide opportunities for both PhD and Honours students with an interest in male reproduction, transgenics, hormonal regulation or developmental biology, noting projects may be tailored to suit the overall interests of research candidates. These projects cover a range of contemporary laboratory techniques; transgenic models, administration and pharmacological suppression of steroids, stereological analysis of cellular changes, microarray analysis, immunohistochemical and molecular biology procedures to evaluate biological actions at the molecular level.
Project 1: The role of steroids and FSH in testicular development.
The overall goal is to study the hormonal regulation of the essential and highly specialised Sertoli cells that support and nurture male germ cell development. A major focus is the postnatal period of FSH-stimulated Sertoli cell proliferation, which determines the final sperm production capacity of mature testes. During Sertoli development there is a switch from very low AR expression at birth to markedly higher expression as proliferation ceases, suggesting final Sertoli differentiation is regulated by temporal androgen activity. This project will use the transgenic FSH and infertile hormone-deficient hypogonadal (hpg) mouse models (1, 2) to compare the postnatal effects of androgen, estradiol and FSH alone or in combination on Sertoli cell proliferation and differentiation, as well as the longer-term spermatogenic consequences of selective postnatal hormone exposure.
Project 2: The molecular pathways activated by testosterone in the testis.
The mechanism of testosterone action in spermatogenesis remains a major enigma in research of testicular function. The AR mediates testosterone effects by regulating androgen-dependent genes, which have yet to be identified in the testis. The conversion of testosterone to more potent DHT (by 5alpha-reductase) or estrogen (by aromatase) may either augment or bypass the AR requirement. We previously found that DHT alone (a non-aromatisable androgen) initiated complete spermatogenesis in hormone-deficient hpg animals. A major goal is to use the androgen-treated hpg model to identify and characterise the genes and signaling pathways activated by testosterone in the testis, using DNA microarray procedures and molecular biology to evaluate global gene expression profiles during the androgen response.
Project 3: Characterisation of a ligand-independent activated FSH receptor.
This project will study a mutated human FSH receptor (FSHR+) first identified in a hypophysectomised male, who unexpectedly remained fertile under treatment with testosterone in spite of undetectable FSH. To investigate the activity of this mutant receptor, we expressed transgenic FSHR+ in the testis of FSH-deficient hpg mice, which revealed FSHR+ stimulated an FSH-like response in the absence of its ligand (3). A short-term project suitable for an honours student will now evaluate the ability of this ligand-independent activated FSHR+ to maintain adult spermatogenesis during induced gonadal regression following hormone withdrawal. Established transgenic models expressing activated FSHR+ or normal FSHR will be used to examine and compare the intratesticular cellular responses and molecular changes induced by this constitutively activated receptor.
For more details, and information about other potential projects, please contact:
Dr Charles Allan
Tel: 9767-9117
Email:
Professor David Handelsman
Tel: 9767-9111
Email:
Relevant publications:
- Haywood, M. et al. (2003) Endocrinology 144: 509-517 [PMID: 12538611]
- Allan, C.M. et al. (2001) Endocrinology 142: 2213-2220. [PMID: 11356665]
- Haywood, M. et al. (2002) Molecular Endocrinology 16: 2582- 2591 [PMID: 12403847