- Email: [email protected]
Relevance of prorenin-renin-angiotensin system to male reproduction
142
R E L E V A N C E OF P R O R E N I N - R E N I N - A N G I O T E N S I N
S Y S T E M TO M A L E R E P R O D U C T I O N
A.K. M u k h o p a d h y a y , J. Cobllanschl, H. M. Behre*, S. Kllesch* and B. Brunswlg-Splckenheler. Instztute for Hormone and Fertlllty Research, Unlverslty of Hamburg, Hamburg and *Institute of R e p r o d u c t l v e Medlclne, W l l h e l m s U n i v e r s i t y of Westfalla, Munster, Germany. The p r o r e n l n - r e n l n - a n g l o t e n s l n s y s t e m (PRAS) is m a l n l y c o n s l d e r e d as a r e g u l a t o r of c a r d i o v a s c u l a r h o m e o s t a s l s . The local o c c u r r e n c e of the c o n s t l t u e n t s of PRAS in m a n y e n d o c r l n e and r e p r o d u c t l v e t i s s u e s has led to a c o n c e p t that P R A S may p l a y a r e g u l a t o r y role In t h e t l s s u e s in w h z c h zt zs expressed. In thzs context, a g r e a t d e a l of z n f o r m a t z o n is a v a l l a b l e on the r o l e of PRAS in the female r e p r o d u c t i v e s y s t e m ( A n d r a d e - G o r d o n et al., B i o c h e m P h a r m a c o l : 4 2 , 715-719, 1991). In contrast, the m a l e r e p r o d u c t l v e s y s t e m v i s - & - v i s P R A S has r e m a i n e d relatlvely less explored. We h a v e r e c e n t l y r e p o r t e d the p r e s e n c e of s l g n i f l c a n t q u a n t l t l e s of p r o r e n i n in h u m a n s e m e n s a m p l e s ( M u k h o p a d h y a y et al., Ann. M e e t l n g of SSR. Ann Arbor, MI. A b s t r a c t 340, 1994). In the p r e s e n t c o m m u n i c a t i o n , we r e p o r t that the p r o r e n z n level in semen is u n d e r t h e r e g u l a t i o n of p i t u i t a r y g o n a d o t r o p h l n slnce the s u p p r e s s i o n of g o n a d o t r o p h i n s in m a l e v o l u n t e e r s by a d m i n i s t e r i n g l o n g a c t l n g a n d r o g e n p r e p a r a t l o n leads to a drop zn semlnal prorenln concentration. The p h y s l o l o g z c a l r e l e v a n c e of seminal p r o r e n l n r e m a i n s still obscure, e x c e p t for the fact that zts c o n c e n t r a t l o n c o r r e l a t e s s z g n l f l c a n t l y w i t h the n u m b e r of sperms per ml of ejaculate, s u g g e s t i n g that p r o r e n i n m a y prove to be an i m p o r t a n t semen parameter.
REGULATION OF UTERi-PLACENTAL PRORENIN A M Pilsner, Univ of Kansas Medical Center, Kansas City, KS 66208, USA Although human uteri-placental tissues had been shown to produce renan-hke actMty as early as 1968, ~ was not untd the 1980's that the substance produced was shown to be mamly the precursor, prorenm (Pro) In view of the fact that Pro can catalyze angtotensm I generation under some conditions, its regulation at extrarenal sates may be of considerable significance Pro and/or its message have been reported to be present in chorion, decldua, and wllous placenta Unhke luxtaglomerular cells, these tissues do not show large amounts of renm-contammg secretory granules and studies have shown that secretion requires new protein synthesis and gene actlvahon. The second messengers which have been found to affect these processes include cychc AMP, calcium and protein kmases A and C The kmehcs of renm secretion are much slower than that from the renal cells and reflect the need for new protein synthesis. Primary signals which modulate Pro secretion from reproductive tissues mclude protein hormones (relaxm, endothehn, HCG) and amines (epinephrine and related pharmacological agents) There is also evidence for negative regulation by anglotensm, endotoxm and cytokmes Recent studies have also implicated cychc GMP, elcosanoids and glucocortlcolds m Pro regulation Some of these regulators may work via autocrme or paracnne signalling and others may act indirectly Since the Pro gene has been found to possess positive and negative regulatory sites, it is anticipated that there are multiple pnmary and secondary stgnalhng mechanisms. Furthermore, since there appear to be multiple cell types which can express Pro, the potential regulation and interactions of the uteri-placental renm-ang=otensm system are lust now beginning to be apprecmted
R E L E V A N C E OF P R O R E N I N - R E N I N - A N G I O T E N S I N
S Y S T E M TO M A L E R E P R O D U C T I O N
A.K. M u k h o p a d h y a y , J. Cobllanschl, H. M. Behre*, S. Kllesch* and B. Brunswlg-Splckenheler. Instztute for Hormone and Fertlllty Research, Unlverslty of Hamburg, Hamburg and *Institute of R e p r o d u c t l v e Medlclne, W l l h e l m s U n i v e r s i t y of Westfalla, Munster, Germany. The p r o r e n l n - r e n l n - a n g l o t e n s l n s y s t e m (PRAS) is m a l n l y c o n s l d e r e d as a r e g u l a t o r of c a r d i o v a s c u l a r h o m e o s t a s l s . The local o c c u r r e n c e of the c o n s t l t u e n t s of PRAS in m a n y e n d o c r l n e and r e p r o d u c t l v e t i s s u e s has led to a c o n c e p t that P R A S may p l a y a r e g u l a t o r y role In t h e t l s s u e s in w h z c h zt zs expressed. In thzs context, a g r e a t d e a l of z n f o r m a t z o n is a v a l l a b l e on the r o l e of PRAS in the female r e p r o d u c t i v e s y s t e m ( A n d r a d e - G o r d o n et al., B i o c h e m P h a r m a c o l : 4 2 , 715-719, 1991). In contrast, the m a l e r e p r o d u c t l v e s y s t e m v i s - & - v i s P R A S has r e m a i n e d relatlvely less explored. We h a v e r e c e n t l y r e p o r t e d the p r e s e n c e of s l g n i f l c a n t q u a n t l t l e s of p r o r e n i n in h u m a n s e m e n s a m p l e s ( M u k h o p a d h y a y et al., Ann. M e e t l n g of SSR. Ann Arbor, MI. A b s t r a c t 340, 1994). In the p r e s e n t c o m m u n i c a t i o n , we r e p o r t that the p r o r e n z n level in semen is u n d e r t h e r e g u l a t i o n of p i t u i t a r y g o n a d o t r o p h l n slnce the s u p p r e s s i o n of g o n a d o t r o p h i n s in m a l e v o l u n t e e r s by a d m i n i s t e r i n g l o n g a c t l n g a n d r o g e n p r e p a r a t l o n leads to a drop zn semlnal prorenln concentration. The p h y s l o l o g z c a l r e l e v a n c e of seminal p r o r e n l n r e m a i n s still obscure, e x c e p t for the fact that zts c o n c e n t r a t l o n c o r r e l a t e s s z g n l f l c a n t l y w i t h the n u m b e r of sperms per ml of ejaculate, s u g g e s t i n g that p r o r e n i n m a y prove to be an i m p o r t a n t semen parameter.
REGULATION OF UTERi-PLACENTAL PRORENIN A M Pilsner, Univ of Kansas Medical Center, Kansas City, KS 66208, USA Although human uteri-placental tissues had been shown to produce renan-hke actMty as early as 1968, ~ was not untd the 1980's that the substance produced was shown to be mamly the precursor, prorenm (Pro) In view of the fact that Pro can catalyze angtotensm I generation under some conditions, its regulation at extrarenal sates may be of considerable significance Pro and/or its message have been reported to be present in chorion, decldua, and wllous placenta Unhke luxtaglomerular cells, these tissues do not show large amounts of renm-contammg secretory granules and studies have shown that secretion requires new protein synthesis and gene actlvahon. The second messengers which have been found to affect these processes include cychc AMP, calcium and protein kmases A and C The kmehcs of renm secretion are much slower than that from the renal cells and reflect the need for new protein synthesis. Primary signals which modulate Pro secretion from reproductive tissues mclude protein hormones (relaxm, endothehn, HCG) and amines (epinephrine and related pharmacological agents) There is also evidence for negative regulation by anglotensm, endotoxm and cytokmes Recent studies have also implicated cychc GMP, elcosanoids and glucocortlcolds m Pro regulation Some of these regulators may work via autocrme or paracnne signalling and others may act indirectly Since the Pro gene has been found to possess positive and negative regulatory sites, it is anticipated that there are multiple pnmary and secondary stgnalhng mechanisms. Furthermore, since there appear to be multiple cell types which can express Pro, the potential regulation and interactions of the uteri-placental renm-ang=otensm system are lust now beginning to be apprecmted