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Steroid Hormone receptors: their intracellular location
TIPS - November 1987 [Vol. 8]
High on the recommended list Pharmacology
by H.P. Rang and M . M . Dale, Churchill Livingstone, 1987. £19.95 (xiv + 736 pages) ISBN 0 443 03407 9 With money burning holes in their pockets, new undergraduates expect to be told precisely what textbooks they should spend it on and are less than h a p p y when staff prevaricate. Nevertheless, we advise students not to make major purchases until after a few hours in the library comparing books which we list as suitable. Our criteria for inclusion (like those for putative CNS neurotransmitters, rarely met in full) are that each text should be comprehensive, accurate and authoritative, as up-to-date as possible with liberal guidelines for further reading and, of paramount importance since otherwise enthusiasm for the subject wanes, readable. This new book will appear very high on our list because it meets these requirements well. Rang and Dale have stylishly written an excellent successor to Schild's Applied Pharmacology. At more than 700 pages it is a longer book, but by no means unweidly. Each double-columned page is set with large type characters which enable quick scanning and easy reading. All diagrams, many in half-tone, are clearly drawn and apposite although the explanatory legends vary in length and cogency. The 36 chapters each end with a list of references to original papers and sensibly chosen review articles or books, most published between 1980 and 1985. A glance at the detailed contents list reveals six major sections. Within General Principles are: a lucid account of mechanisms of drug action, taking the reader beyond the receptor to intracellular events; an excellent chapter on measurement, featuring principles and examples of biological and chemical assays; and a concise description of absorption,
451
distribution and fate of drugs with a superficial treatment of pharmacokinetics. Chemical Mediators aptly brings together peripheral nervous systems and local hormones in a lengthy section befitting a cornerstone in rational drug development. About half the book is taken up with Major Organ Systems and the Central Nervous System, logically and readably presented with emphasis, where possible, on relating mechanisms of drug action to knowledge of endogenous substances and on speculations about future developments. The text is completed with comparatively short sections on Chemotherapy, including anticancer and antimicrobial drugs and General Topics, in which appear nontherapeutic agents and drug toxicity. In attempting to produce a comprehensive text without superfluity, some omissions or inaccur-
Steroids in the nuclear zone Steroid Hormone Receptors: Their IntraceUular Location
edited by C. R. Clark, Verlags Gesellschaft, 1987. DM125/$83.00 (vii + 277 pages) ISBN 3 527 26471 X This book critically examines evidence for the intracellular location of steroid hormone receptors: are these receptors located entirely in the nucleus or are some receptors located in the cytoplasm? To answer this question, leading authorities in the area have come together and provide a convincing case for the new concept that steroid hormone receptors are almost entirely located in the nucleus. The strongest evidence comes in the last chapter of the book which deals with the immunocytochemical staining of estrogen-responsive cells with monoclonal antibody for the estrogen receptor (Press and Greene). This powerful technique clearly indicates that the vast proportion of receptors are located in the nucleus. Similar results are described for the androgen and
acies are inevitable but fortunately they are rare. For instance, the development of dichloroisoprenaline is wrongly attributed to Black et al. in 1958; EDRF, released from vascular endothelium by a n u m b e r of drugs to mediate vasodilation, is m e n t i o n e d in two sections but not indexed; the chemical formula of muscarine is wrong; among the prostaglandins, PGD2 was underemphasized; in view of its topicality there was surprisingly no mention of the h u m a n immunodeficiency virus (nor other retroviruses) so that possibilities for the treatment of AIDS were ignored. However, such minor criticisms should not detract from the value of Pharmacology, which is a first-rate textbook suitable both for science and pre-clinical medical students. In a few years time, staff and students may look forward eagerly to the next edition, a sure sign of a textbook's popularity and commercial success. B. J. L A R G E
Department of Pharmacology, Worsley Medical and Dental Building, The University, Leeds LS2 9JT, UK.
progesterone receptors while conflicting data exists for the intracellular location of the glucocorticoid receptor. If the most convincing evidence is offered in the final chapter what about the rest of the book? The first chapter is most appropriately written by Elwood Jensen. Although the new location of steroid hormone receptors argues against the classical two-step model of receptor occupancy and translocation to the nucleus, Jensen argues convincingly that without the isolation of the 'cytoplasmic receptor' steroid-induced activation of the receptor may have gone undetected. In other chapters evidence for the nuclear origin of the receptors is provided by alternative approaches. For example, in the chapter of Welshons and Jordan, they describe their work using cytochalasin B to form nucleoplasts and cytoplasts of estrogenresponsive pituitary (GH3) cells. In such studies estrogen receptors were located entirely in the nucleoplasts. Studies by Sheridan in Chapter 8 not only provide supporting evidence of the nuclear
452
TIPS - November 1987 [Vol. 8]
location of the receptor but indicate that leakage from the nucleus d u r i n g h o m o g e n i z a t i o n was the reason w h y for over a decade, the receptors were detected in the cytosol. N e w questions concerning steroid h o r m o n e action are raised by the nuclear location of all steroid receptors. For example: h o w does the steroid h o r m o n e make its w a y from the plasma m e m b r a n e to the nucleus? W h a t prevents the steroid from b e i n g extensively metabolized en route to the nucleus? H o w can w e explain the m e c h a n ism of action of steroid h o r m o n e antagonists? Does receptor recycling occur and h o w is it regulated? The last two questions are i m p o r tant, since it has been postulated that steroid h o r m o n e antagonists p r o m o t e nuclear retention of the
receptor and p r e v e n t their recycling. This is clearly not the case if all the receptor is located in the nucleus to begin with! Although these questions are raised in the book, no answers are given and this could be perceived as a weakness. What the book does d e v o t e time to is the next step in the m e c h a n ism of steroid h o r m o n e action. It addresses the nature of the nuclear acceptor sites for the occupied and u n o c c u p i e d receptors. Evelyn Barrack offers a nice account of her work, w h i c h implicates proteins of the nuclear protein matrix as b e i n g involved in the acceptor mechanism. Strong points of the b o o k are the extensive titled references given at the end of each chapter. In some of these instances, refer-
ences are given to the most current literature. This suggests that considerable effort has b e e n m a d e to p r o m o t e the rapid publication of this book. The editor and p u b l i s h e r should be a p p l a u d e d for this effort, and this makes the more than unusual n u m b e r of typographical errors acceptable. In s u m m a r y , this b o o k p r o v i d e s an excellent account of the n e w concept in steroid h o r m o n e action - that all receptor is nuclear and that no translocation occurs. I can strongly r e c o m m e n d it to every researcher in the steroid h o r m o n e receptor field and I feel that it will be an assset to those w h o w o r k in the area. TREVOR M. PENNING Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
lB~tm~ al
Structure--activity relationships of o m e p r a z o l e a n a l o g u e s a n d their m e c h a n i s m of action, by Per Lindberg, Arne Br~ndstr6m and Bj6rn Wallmark. (October 1987, pp. 399--402) The adjacent structure should have b e e n incorporated into Table I to indicate the points of substitution. We apologise for this error.
N . r - W H
THE M O D E R N A P P R O A C H TO C L A S S I C A L RESEARCH
Polm~ence
Harbour Estate Sheerness. Kent,
CH2
ME12
;RZ
DRUG BIOASSAY SYSTEMS FOR PHARMACOLOGY RESEARCH
Tel: ( 0 7 9 , 5 ) 6 6 7 5 5 1 Telex. 965088
Represented 50 countries
m o-.'~r
AUSTRALIA AuMrallar~ Sctenhfic h]s~rum~Nt~ GPO B o x 1821 AdeJa~d~ 5001 S o u t h AuMraha Tel 356 6996 T]x 8 8 7 6 5 Ref ADIO00 FRANCE Phvm~,u S A R L 2; ~{J~ (1(, (; ~rh[)o-[ orrtu~} T*
?50302
AH Ph,,tr*,[,
GERMANY
W{,~t G e r m ; { r y t~, H5~80 ~ t
[~,1 ();, 11 ~, 6,:) c,!
.JAPAN 3 N l h o n h ; ~ s h i - M u t { J m m h, (:h[Jo KL, Tokyo I0;{ ,Japdr, fPi 01 241 2444 r]~ ~ , ~ , i 1 U.S.A
and
CANADA
P e q u a n n o o ( N J 0 7 4 4 0 [J S tel ~0;'!~ 6 9 4 0 ' ) 0 0 r l , :,t*;~'/~
• Design the system to suit your requirements. • Versatile, low cost, modular jacketed systems and tissue bath assemblies. • A wide variety of specialised glassware. • Low cost, high precision, transducer positioners. • Corrosion resistant laboratory scaffolding and clamping products. • A wide range of supporting instrumentation including: Transducers, Amplifiers, Stimulators and Chart Recorders.
~ii~!i~{: i.~-i~ ........ :..............::
/:i
/
l
FURTHER DETAILSARE AVAILABLEUPON REQUEST. Enter advertising enquiry number 116 on advertising enquiry form
High on the recommended list Pharmacology
by H.P. Rang and M . M . Dale, Churchill Livingstone, 1987. £19.95 (xiv + 736 pages) ISBN 0 443 03407 9 With money burning holes in their pockets, new undergraduates expect to be told precisely what textbooks they should spend it on and are less than h a p p y when staff prevaricate. Nevertheless, we advise students not to make major purchases until after a few hours in the library comparing books which we list as suitable. Our criteria for inclusion (like those for putative CNS neurotransmitters, rarely met in full) are that each text should be comprehensive, accurate and authoritative, as up-to-date as possible with liberal guidelines for further reading and, of paramount importance since otherwise enthusiasm for the subject wanes, readable. This new book will appear very high on our list because it meets these requirements well. Rang and Dale have stylishly written an excellent successor to Schild's Applied Pharmacology. At more than 700 pages it is a longer book, but by no means unweidly. Each double-columned page is set with large type characters which enable quick scanning and easy reading. All diagrams, many in half-tone, are clearly drawn and apposite although the explanatory legends vary in length and cogency. The 36 chapters each end with a list of references to original papers and sensibly chosen review articles or books, most published between 1980 and 1985. A glance at the detailed contents list reveals six major sections. Within General Principles are: a lucid account of mechanisms of drug action, taking the reader beyond the receptor to intracellular events; an excellent chapter on measurement, featuring principles and examples of biological and chemical assays; and a concise description of absorption,
451
distribution and fate of drugs with a superficial treatment of pharmacokinetics. Chemical Mediators aptly brings together peripheral nervous systems and local hormones in a lengthy section befitting a cornerstone in rational drug development. About half the book is taken up with Major Organ Systems and the Central Nervous System, logically and readably presented with emphasis, where possible, on relating mechanisms of drug action to knowledge of endogenous substances and on speculations about future developments. The text is completed with comparatively short sections on Chemotherapy, including anticancer and antimicrobial drugs and General Topics, in which appear nontherapeutic agents and drug toxicity. In attempting to produce a comprehensive text without superfluity, some omissions or inaccur-
Steroids in the nuclear zone Steroid Hormone Receptors: Their IntraceUular Location
edited by C. R. Clark, Verlags Gesellschaft, 1987. DM125/$83.00 (vii + 277 pages) ISBN 3 527 26471 X This book critically examines evidence for the intracellular location of steroid hormone receptors: are these receptors located entirely in the nucleus or are some receptors located in the cytoplasm? To answer this question, leading authorities in the area have come together and provide a convincing case for the new concept that steroid hormone receptors are almost entirely located in the nucleus. The strongest evidence comes in the last chapter of the book which deals with the immunocytochemical staining of estrogen-responsive cells with monoclonal antibody for the estrogen receptor (Press and Greene). This powerful technique clearly indicates that the vast proportion of receptors are located in the nucleus. Similar results are described for the androgen and
acies are inevitable but fortunately they are rare. For instance, the development of dichloroisoprenaline is wrongly attributed to Black et al. in 1958; EDRF, released from vascular endothelium by a n u m b e r of drugs to mediate vasodilation, is m e n t i o n e d in two sections but not indexed; the chemical formula of muscarine is wrong; among the prostaglandins, PGD2 was underemphasized; in view of its topicality there was surprisingly no mention of the h u m a n immunodeficiency virus (nor other retroviruses) so that possibilities for the treatment of AIDS were ignored. However, such minor criticisms should not detract from the value of Pharmacology, which is a first-rate textbook suitable both for science and pre-clinical medical students. In a few years time, staff and students may look forward eagerly to the next edition, a sure sign of a textbook's popularity and commercial success. B. J. L A R G E
Department of Pharmacology, Worsley Medical and Dental Building, The University, Leeds LS2 9JT, UK.
progesterone receptors while conflicting data exists for the intracellular location of the glucocorticoid receptor. If the most convincing evidence is offered in the final chapter what about the rest of the book? The first chapter is most appropriately written by Elwood Jensen. Although the new location of steroid hormone receptors argues against the classical two-step model of receptor occupancy and translocation to the nucleus, Jensen argues convincingly that without the isolation of the 'cytoplasmic receptor' steroid-induced activation of the receptor may have gone undetected. In other chapters evidence for the nuclear origin of the receptors is provided by alternative approaches. For example, in the chapter of Welshons and Jordan, they describe their work using cytochalasin B to form nucleoplasts and cytoplasts of estrogenresponsive pituitary (GH3) cells. In such studies estrogen receptors were located entirely in the nucleoplasts. Studies by Sheridan in Chapter 8 not only provide supporting evidence of the nuclear
452
TIPS - November 1987 [Vol. 8]
location of the receptor but indicate that leakage from the nucleus d u r i n g h o m o g e n i z a t i o n was the reason w h y for over a decade, the receptors were detected in the cytosol. N e w questions concerning steroid h o r m o n e action are raised by the nuclear location of all steroid receptors. For example: h o w does the steroid h o r m o n e make its w a y from the plasma m e m b r a n e to the nucleus? W h a t prevents the steroid from b e i n g extensively metabolized en route to the nucleus? H o w can w e explain the m e c h a n ism of action of steroid h o r m o n e antagonists? Does receptor recycling occur and h o w is it regulated? The last two questions are i m p o r tant, since it has been postulated that steroid h o r m o n e antagonists p r o m o t e nuclear retention of the
receptor and p r e v e n t their recycling. This is clearly not the case if all the receptor is located in the nucleus to begin with! Although these questions are raised in the book, no answers are given and this could be perceived as a weakness. What the book does d e v o t e time to is the next step in the m e c h a n ism of steroid h o r m o n e action. It addresses the nature of the nuclear acceptor sites for the occupied and u n o c c u p i e d receptors. Evelyn Barrack offers a nice account of her work, w h i c h implicates proteins of the nuclear protein matrix as b e i n g involved in the acceptor mechanism. Strong points of the b o o k are the extensive titled references given at the end of each chapter. In some of these instances, refer-
ences are given to the most current literature. This suggests that considerable effort has b e e n m a d e to p r o m o t e the rapid publication of this book. The editor and p u b l i s h e r should be a p p l a u d e d for this effort, and this makes the more than unusual n u m b e r of typographical errors acceptable. In s u m m a r y , this b o o k p r o v i d e s an excellent account of the n e w concept in steroid h o r m o n e action - that all receptor is nuclear and that no translocation occurs. I can strongly r e c o m m e n d it to every researcher in the steroid h o r m o n e receptor field and I feel that it will be an assset to those w h o w o r k in the area. TREVOR M. PENNING Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
lB~tm~ al
Structure--activity relationships of o m e p r a z o l e a n a l o g u e s a n d their m e c h a n i s m of action, by Per Lindberg, Arne Br~ndstr6m and Bj6rn Wallmark. (October 1987, pp. 399--402) The adjacent structure should have b e e n incorporated into Table I to indicate the points of substitution. We apologise for this error.
N . r - W H
THE M O D E R N A P P R O A C H TO C L A S S I C A L RESEARCH
Polm~ence
Harbour Estate Sheerness. Kent,
CH2
ME12
;RZ
DRUG BIOASSAY SYSTEMS FOR PHARMACOLOGY RESEARCH
Tel: ( 0 7 9 , 5 ) 6 6 7 5 5 1 Telex. 965088
Represented 50 countries
m o-.'~r
AUSTRALIA AuMrallar~ Sctenhfic h]s~rum~Nt~ GPO B o x 1821 AdeJa~d~ 5001 S o u t h AuMraha Tel 356 6996 T]x 8 8 7 6 5 Ref ADIO00 FRANCE Phvm~,u S A R L 2; ~{J~ (1(, (; ~rh[)o-[ orrtu~} T*
?50302
AH Ph,,tr*,[,
GERMANY
W{,~t G e r m ; { r y t~, H5~80 ~ t
[~,1 ();, 11 ~, 6,:) c,!
.JAPAN 3 N l h o n h ; ~ s h i - M u t { J m m h, (:h[Jo KL, Tokyo I0;{ ,Japdr, fPi 01 241 2444 r]~ ~ , ~ , i 1 U.S.A
and
CANADA
P e q u a n n o o ( N J 0 7 4 4 0 [J S tel ~0;'!~ 6 9 4 0 ' ) 0 0 r l , :,t*;~'/~
• Design the system to suit your requirements. • Versatile, low cost, modular jacketed systems and tissue bath assemblies. • A wide variety of specialised glassware. • Low cost, high precision, transducer positioners. • Corrosion resistant laboratory scaffolding and clamping products. • A wide range of supporting instrumentation including: Transducers, Amplifiers, Stimulators and Chart Recorders.
~ii~!i~{: i.~-i~ ........ :..............::
/:i
/
l
FURTHER DETAILSARE AVAILABLEUPON REQUEST. Enter advertising enquiry number 116 on advertising enquiry form