GROUP LEADER: Prof. Pieter Swart
Office: A115 JC Smuts Building
Molecular and cellular steroidogenesis
Molecular and cellular steroidogenesis is a study of the tissues and enzymes involved in the biosynthesis of steroid hormones. These hormones are responsible for normal sexual development and behaviour and ultimately reproduction in all mammals. The steroids also control our metabolic responses to stress (drought, hunger, mental stress and illness) and regulate mineral and water balance in the body. From this summary it is clear that these enzymes play an important role in the regulation of normal mammalian physiology.
I am part of a well established steroid research group in the Department of Biochemistry here at the University of Stellenbosch. We are currently investigating two unique South African problems directly related to adrenal steroidogenesis. These two projects are:
The influence of natural pant products on mammalian adrenal steroidogenesis
The indigenous Namibian shrub, Salsola tuberculatifromis Botsch., prolongs gestation in Karakul sheep. Investigation of the active compounds in the shrub showed that the plant had contraceptive properties and the ability to interact with the normal physiological balance of the steroid hormone, cortisol, which is responsible for mammalian stress responses as described above. The active compounds in the shrub have been shown by our group to interact with adrenal steroidogenic cytochorme P450 dependent enzymes. These compounds are therefore important leads for naturally occurring contraceptives, anti-stress agents and anti-inflamtories and have enormous economic potential for Southern Africa. In order to study, evaluate and identify new active plant products a fundamental knowledge of the steroidogenic enzymes involved in normal steroid hormone production is required. In my laboratory we are currently extracting compounds from S. tuberculatiformis and testing the activity on the adrenal steroidogenic cytochromes P450.
The role of adrenal steroidogenesis in the inability of the Angora goat to cope with stress.
South African Angora goat (Capra aegagrus) is the most efficient fibre producing, but least hardy small stock breed in Southern Africa. South Africa produces approximately 15 million kg mohair annually of which more than 95% exported. Frequent and severe losses of young and newly shorn Angora goats occur during cold spells. The simultaneous death of thousands of animals has severe financial implications for the industry. We showed that the Angora adrenal gland does not produce the steroid, cortisol, in sufficient amounts to maintain normal energy balance in the animal during cold spells. Work is currently underway to identify and study the cytochrome P450-dependent enzymes involved in this adrenal dysfunction with the ultimate goal to identify and breed more hardy goats that will not be susceptible to stress. To fully understand and identify the causes of adrenal dysfunction in the Angora goat, the genetic as well as a catalytic activities of these enzymes will be fully characterised.
Membrane applications for the monitoring and improvement of water quality
The first reports of synthetic compounds that could interfere with the normal physiological functioning of the endocrine system in mammals, amphibians and reptiles was made in 1958. The physiological effects of these compounds, later collectively named endocrine disrupting compounds (EDC's), were observed in lakes, rivers and surface waters in Northern America and subsequently in Europe. Initial investigations focussed on the effect of these substances on the reproductive systems and sexual differentiation of various aquatic species, but it later became apparent that these compounds also found their way into drinking water where it could severely affect the hormonal balance in man leading to feminization and sterility. A hallmark of EDC contamination is the low concentrations (lower than ppm levels) in which these substances can occur in various water sources. This phenomenon made it extremely difficult to prove that these type of compounds existed at all and, in addition, severely hampered the acceptance of an EDC cause and effect chain. Several case studies, and the employment of more sensitive biological and physical measuring techniques have, however, gone a long way to dispel any doubts about the presence and negative physiological consequences of EDC's in water sources used for domestic as well as recreational purposes. In addition an awareness of the potential disastrous effects these compounds can have on bird and animal life, as well as total ecosystems, is slowly growing and more funds are being made available world wide to investigate the EDC phenomenon.
Despite the rapid development of biological and physico chemical detection and screening techniques, the low concentrations in which most EDC's occur in the different water sources, is severely hampering the indication of these compounds. It is therefore important to continue the search for more sensitive and reproducible assays for these substances. These type of studies, and the techniques that are developed from them are, however, often complicated, extremely expensive and technically demanding to execute. A supplementary approach to the problem would be to devise a method to selectively concentrate EDC's up to a level where standard techniques would be able to measure the amounts accurately and reproducibly. In addition a simple colorimetric system with a low skills requirement, for the semi-qualitative indication of EDC's would be useful as a routine test for large water suppliers as well as "spot" checks in rural and remote areas where sophisticated technology is not readily available. We are currently developing a membrane based rapid and unsophisticated screening system for EDC's in drinking water using the thyroid and oestrogen receptors as model affinity ligands to capture and concentrate potential EDC's for detection by a colorimetric method.