中国体育彩票

????GROEPLEIER:  Prof. Pieter Swart

Posisie: Emeritus Professor

Kantoor             A115 JC Smuts Building

Foon:               +27-(0)21-808-5865/62/77

Faks:                +27-(0)21-808-5863

Epos:               pswart@sun.ac.za

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 中国体育彩票 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.??

Membraantoepassings vir die monitering en verbetering van water kwalitieit

Die eerste verslae van sintetiese verbindings, wat met die normale fisiologiese funksionering van die endokriene stelsel in soogdiere, amfibie? en reptiele kan inmeng, is in 1958 gemaak. Die fisiologiese effekte van hierdie verbindings, later gesamentlik genoem hormoonversteurings-verbindings (EDCs na Endocrine Disrupting Compounds), is in mere, riviere en oppervlakwaters in Noord-Amerika en daarna ook in Europa waargeneem. Die fokus van aanvanklike ondersoeke was op die uitwerking van hierdie stowwe op die reproduktiewe stelsels en seksuele differensiasie van verskeie akwatiese spesies. Dit het later duidelik geword dat hierdie verbindings ook hul pad na drinkwater gevind het, waar dit die hormonale balans in die mens drasties kon be?nvloed en aanleiding kon gee tot feminisering en selfs steriliteit. 'n Kenmerk, en besondere probleem, van EDC-besoedeling is die lae konsentrasies (laer as dpm vlakke) waarin hierdie stowwe in verskillende waterbronne kan voorkom. Hierdie verskynsel het dit baie moeilik gemaak om te bewys dat hierdie tipe verbindings werklik bestaan en die aanvaarding van EDCs as 'n gesondheidsrisiko ernstig belemmer. Verskeie gevallestudies, en die gebruik van meer sensitiewe biologiese- en fisiese analitiese tegnieke, het daar toe bygedra om enige twyfel oor die teenwoordigheid en negatiewe fisiologiese gevolge van EDCs in waterbronne, wat aangewend word vir huishoudelike sowel as ontspanningsdoeleindes, uit die weg te ruim. Hiermee saam het die bewustheid van die potensi?le rampspoedige gevolge wat hierdie verbindings op die reproduksie van vo?ls en diere, sowel as totale ekostelsels kan hê, stadig gegroei en meer fondse is wêreldwyd beskikbaar gestel om die EDC-verskynsel te ondersoek.

Ten spyte van die vinnige ontwikkeling van biologiese- en fisies-chemiese opsporingstegnieke word die opsporing van EDCs in die verskillende waterbronne waar dit voorkom baie bemoeilik a.g.v. die lae konsentrasies waarin die meeste van hierdie tipe verbindings aanwesig is. Dit is dus belangrik om met die soeke na meer sensitiewe en reproduseerbare toetse vir EDCs voort te gaan. Hierdie studies, en die tegnieke wat daar uit ontwikkel is, is dikwels ingewikkeld, baie duur en tegnies veeleisende om uit te voer. 'n Aanvullende benadering tot die probleem sou wees om 'n metode te ontwikkel wat EDCs selektief kan konsentreer tot 'n vlak waar standaard tegnieke in staat sou wees om die verbindings akkuraat en reproduseerbaar te bepaal. Daarbenewens sal 'n eenvoudige kolorimetriese stelsel, met 'n lae vaardigheidsvereiste, nuttig wees vir die semi-kwalitatiewe bepaling van EDCs as 'n roetine-toets vir groot waterverskaffers. Die sisteem sou ook gebruik kon word om vooraf bepalings te doen in landelike en afgele? gebiede waar gesofistikeerde tegnologie is nie geredelik beskikbaar nie. Ons is tans besig om 'n membraangebaseerde vinnige en ongesofistikeerde sisteem vir die bepaling van EDCs in drinkwater te ontwikkel. Deur gebruik te maak van 'n ge?mmobiliseerde estrogeenreseptor as model, word ligande vir hierdie reseptor gekonsentreer en bied dit die potensiaal vir die opsporing van EDCs m.b.v 'n kolorimetriese metode.??