Professor Janet Hapgood
Affiliations
- Full Member, Institute of Infectious Disease and Molecular Medicine
Key Expertise
Molecular Medicine
Main Research Focus
Professor Hapgood's field is broadly in intracellular molecular mechanisms of action of steroid receptors, in particular the glucocorticoid receptor (GR). Research is focussed on ligand-selectivity, regulation of gene expression as well as cross talk between steroid receptors and other signalling pathways, which allows functional integration between stress, reproduction and immune function. This research is conducted in the broad context of reproduction, inflammation, contraception and infectious disease, in particular HIV-1. Different progestins are used in contraception. MPA, widely used as an injectable contraceptive in Sub-Saharan Africa, has been reported in observational clinical studies to increase HIV-1 acquisition, unlike another injectable contraceptive NET-EN. The Hapgood lab is investigating the molecular basis for this difference. Broadly, the lab is investigating the mechanisms and effects on immune function and HIV-1 pathogenesis of different progestin contraceptives via the GR, as well as cross talk between the GR and other receptors, and the role of the unliganded GR. The effects of different progestins via different steroid receptors, as well as their metabolism, are also being investigated. Reciprocal modulation of progestins and ARVs is another area of interest, with a view to choice of combination therapies to inhibit both HIV-1 acquisition and pregnancy. The work on HIV and contraceptives is highly relevant to women’s choice of contraception in areas of high risk of HIV-1 infection in Sub-Saharan Africa and South Africa in particular.
Most Significant Paper Authored in 2024
Avenant, C., Singata-Madliki, M., Bick, A. J., Africander, D., Balakrishna, Y., Storbeck, K. H., Moliki, J. M., Dlamini, S., Skosana, S., Smit, J., Beksinska, M., Beesham, I., Seocharan, I., Batting, J., Hofmeyr, G. J., & Hapgood, J. P. (2024).
HIV acquisition risk with norethisterone (NET) enanthate (NET-EN) is reportedly less than for depo[1]medroxyprogesterone acetate intramuscular (DMPA-IM). We investigated the effects of these progestin[1]only injectable contraceptives on serum testosterone and sex hormone binding globulin (SHBG) levels, since these may play a role in sexual behavior and HIV acquisition. Results show a substantial and differential decrease in testosterone and SHBG levels for both contraceptovs. This does not explain our previous finding of no detected decrease in risky sexual behavior or sexual function for DMPA-IM or NET[1]EN users from D0 to 25W. Medroxyprogesterone (MPA) and NET are androgenic and are both present in molar excess over testosterone and SHBG concentrations at 25W. Any within or between contraceptive group androgenic effects on behavior in the brain are likely dominated by the androgenic activities of MPA and NET and not by the decreased endogenous testosterone levels.