Clinical Endocrinology
  & Metabolism

 
     
 

Research Trial:
Prince Henry's Institute is seeking non-smoking, healthy but overweight men aged 40-70 years for a study of testosterone treatment on body fat and cardiovascular disease.

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Research Projects

Projects Supervisor:

Dr Peter Stanton
Honorary Lecturer in Biochemistry,
Monash University
Phone: 9594 4389
Email: peter.stanton@princehenrys.org

1. Identification of inhibin B binding proteins in pituitary, ovarian and testicular cell lines

Inhibin exists as two forms (inhibin A and B) which appear to share similar biological activities however they are expressed in different tissues and appear to operate through different receptors. While information is available about inhibin A binding sites there is limited information about how inhibin B binds to its receptor. The objective of this study is to characterise in terms of affinity, specificity and molecular size the inhibin B binding proteins present in a variety of cell lines thought to contain inhibin B receptors.

2. Characterisation of modified forms of inhibin

A number of modified inhibin forms have now been identified however their biological activity are unknown.
a) In a collaborative study with Dr Andrew Shelling, Auckland University we are investigating a modified inhibin form identified in a subgroup of women with premature ovarian failure. We are proposing to produce this modified inhibin form by recombinant methodologies and test its biological activity
b) inhibins in serum and amniotic fluid from pregnant women contain inhibin forms about half the size of normal inhibins. Are these important?

3. Characterisation of inhibin A receptor

We have now shown that inhibin A binds to a series of cell-surface binding proteins in cell lines derived from the testis. One or more of these proteins is thought to be the inhibin receptor(s). The aim of this project is to characterise these proteins and establish their importance as inhibin signalling proteins. Methodologies include cell culture, immunoprecipitation, SDS-PAGE, Western blotting, autoradiography, HPLC.

4. Inhibin and ovarian cancer

Inhibin A and B are produced and secreted by several ovarian cancers. Monitoring serum levels by immunoassay may be a useful diagnostic aid in the initial assessment of this disease and in monitoring its potential recurrence following surgery. The assays are applicable to women after menopause when the majority of ovarian cancers are detected and when the normal ovarian production of inhibin is low to negligible. A new inhibin immunoassay (total inhibin ELISA) has been developed with the intention of widespread clinical application. The assay readily detects granulosa cell and mucinous tumours. CA125, a widely used ovarian cancer marker, detects the other main ovarian cancer types (serous, endometrioid, undifferentiated) with high sensitivity. The combination of the two tests detects the majority of ovarian cancers with high specificity (95%) and sensitivity (95%). The total inhibin test is now being marketed by a US diagnostics company (DSLabs Inc, Webster, Texas) and is currently being modified for the commercial diagnostic laboratories. Various studies are proposed to assess if the combined test is suitable for early detection of the disease.

5. Proteins involved in sperm release

Supervisors: Dr Liza O'Donnell and Dr Kyriakos Pratis
Our research into the regulation of sperm production have identified that the process of sperm release (spermiation) is affected when male hormonal contraceptives are given. Contraceptives that specifically and completely inhibit this process would be highly effective and have limited side effects and therefore we are mapping the molecular events involved in spermiation. Research projects are available in this area using a variety of molecular biological and proteomic techniques.





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