Proceedings of the 1985 Laurentian Hormone Conference

772 Pages·1986·16.979 MB·English

by  Roy O. Greep (Eds.)

RECENT PROGRESS IN
HORMONE RESEARCH
Proceedings of the
1985 Laurentian Hormone Conference
Edited by
ROY O. GREEP
VOLUME 42
PROGRAM COMMITTEE
G. D. Aurbach I. A. Kourides
J. D. Baxter A. R. Means
J. C. Beck J. E. Rail
J. H. Clark N. B. Schwartz
H. Friesen J. L. Vaitukaitis
R. O. Greep W. W. Vale
P. A. Kelly
1986
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LIST OF CONTRIBUTORS AND DISCUSSANTS
C. E. Ahmed F. Esch
B. D. Albertson W. S. Evans
T. Andreone B. Everitt
G. Anogianakis P. Feuillan
S. Asa L. A. Fitzpatrick
S. A. Atlas CM. Foster
G. D. Aurbach D. L. Foster
A. Baird M. W. Freeman
C. W. Bardin H. G. Friesen
K. M. Barnes L. Frohman
E. Beale D. Funkenstein
J. C. Beck R. Furlanetto
H. P. J. Bennett H. B. Garcia
R. Billard J. Geller
R. M. Blizzard J. R. Gill
P. Bohlen J. W. Godsall
J. L. C. Borges M. Goldstein
H. L. Bradlow D. Goltzman
S. J. Brand J. Gorski
M. L. Brandi D. K. Granner
W. J. Bremner P. Greengard
A. E. Broadus R. Greep
C. Brook M. A. Gréer
W. J. Burtis M. M. Grumbach
G. Callard R. Guillemin
I. Callard J. Hansen
G. T. Campbell C. Hart
C. Campen H. Hemmings
R. M. Carey K. D. Hench
M. Caruso-Nicoletti J. M. Hershman
F. G. Cassorla N. J. Hickok
J. F. Catterall L. A. Hinds
J. P. Chang K. Ho
T. T. Chen R. A. Hoffman
J. H. Clark T. Hökfelt
S. Cohen T. Horton
F. Comité E. Horvath
M. J. Cronin A.-L. Hulting
C. Cuello T. Igarashi
G. B. Cutler, Jr. K. L. Insogna
G. Delahunty O. A. Jänne
B. M. Dobyns O. Johansson
M. W. Draper S. L. Kaplan
W. D. Drucker F. J. Karch
B. Eckstein J. Kassis
IX
X CONTRIBUTORS
M. S. Katz R. Osathanondh
D. L. Keefe C. Ouimet
R. P. Kelch H. Papkoff
P. A. Kelly 0. H. Pescovitz
T. M. Kelly R. E. Peter
D. Kenigsburg D. K. Pomerantz
G. J. Klingensmith J. T. Potts, Jr.
E. Knobil S. A. Rabbani
K. K. Kontula M. Raj
M. Koutsilieris J. E. Rail
K. Kovacs S. Reichlin
H. M. Kronenberg B. F. Rice
H. Kulin R. Rittmaster
R. F. Laherty J. Ri vier
J. M. Lakoski C. T. Roberts, Jr.
L. Laue J. Robinson
K. Lederis A. D. Rogol
Y. A. Lefevre J. L. Ross
D. A. Leong J. Roth
D. LeRoith M. F. Rouleau
M. A. Lesniak K. D. Ryan
N. Ling R. Ryan
L. M. Long M. Saffran
D. L. Loriaux D. Sakai
J. M. Lundberg N. Samaan
T. Maack K. Sasaki
G. J. MacDonald M. Schalling
R. M. MacLeod E. A. Schriock
S. J. McConnell N. B. Schwartz
A. Means B. A. Scoggins
B. Meister G. Segre
T. Melander S. Sen
E. Melanitou P. J. Seppänen
M. H. Meiner J. Shemer
L. A. Meserve M. R. Sherman
J. Mitchell S. H. Shih
R. O. Morgan J. Shiloach
P. Mormède J. Shull
D. J. Morris P. Singh
L. Murphy M. C. Skerda
C.S. Nahorniak P. Smith
M. V. Nekola M. Sokolowska
M. I. New 1. M. Spitz
C. S. Nicoli G. Stack
J. M. Nolin A. F. Stewart
W. D. Odell D. R. Stewart
S. R. Ojeda J. F. Tait
T. Okazaki E. Terasawa
D. H. Olster M. O. Thorner
R. J. Omeljaniuk C. H. Tyndale-Biscoe
CONTRIBUTORS
N. Ueno M. Walters
H. F. Urbanski C. S. Watson
M. Uriarte W. B. Wehrenberg
W. Vale W. V. Welshons
M. L. Vance S. Werner
W. VanderLaan G. L. Wilson
P. Vecsei K. M. Wiren
J. D. Veldhuis S. M. Yellon
I. Walaas S.-Y. Ying
J. Walent K. Yoshinaga
PREFACE
This volume of Recent Progress in Hormone Research (the thirteenth
and last for which I shall serve as editor) is another in this serial publica­
tion based on the proceedings of the Laurentian Hormone Conference
held in September 1985 in Banff, Alberta, Canada. The topics discussed
were of timely and varied interest. They covered the latest developments
in research on such important topics as chemical neuroanatomy of the
brain based on the histochemistry of brain neuronal transmitters and pep-
tides; hormonal regulation of gene transcription and expression; steroid
hormone receptors and their action; the atrial naturietic factor; the fibro-
blast growth factor; neuroendocrinology of puberty in rodents, seasonal
breeders, and humans; comparative endocrinology including studies on
marsupials, teleosts, and microorganisms; and parathyroid hormone,
bioactive forms, gene expression, and malignancy-associated hypercalce-
mia. These subjects have been covered by leading experts in their special
fields, and readers will find up-to-the-minute information in every in­
stance.
I wish to convey my gratitude and that of the Program Committee to the
following persons who served so ably as chairpersons of the several ses­
sions of this conference: Drs. Anthony R. Means, Robert J. Ryan,
J. Edward Rail, Adolfo de Bold, James H. Clark, Jr., Selna L. Kaplan,
Charles S. Nicoli, Robert M. Blizzard, and Gerald D. Aurbach. Our
appreciation and admiration are due to Lucy Felicissimo and Linda Car-
sagnini for their prompt and skillful transcription of the taped discussions.
It is also a pleasure to acknowledge our grateful appreciation of the fine
relations we have had with the staff of Academic Press over the past
years.
I am pleased and proud to wish my successor, Dr. James H. Clark, the
same sense of satisfaction that I have derived from fostering this re­
nowned publication.
Roy O. Greep
XUl
RECENT PROGRESS IN HORMONE RESEARCH, VOL. 42
Neurons with Multiple Messengers with Special Reference
to Neuroendocrine Systems1
TOMAS HÖKFELT,* BARRY EvERiTT,t BJÖRN MEISTER,*
TOR MELANDER,* MARTIN SCHALLING,* OLLE JOHANSSON,*
JAN M. LUNDBERG,$ ANNA-LENA HULTING,§ SIGBRITT WERNER,§
CLAUDIO CUELLO,** HUGH HEMMINGS,^ CHARLES ΟΙΠΜΕΤ,Φ
IVAR WALAAS,$ PAUL GREENGARD,Î AND MENEK GOLDSTEINÎÎ
* Departments of Histology and t Pharmacology, Karolinska Institutet, § Department of
Endocrinology, Karolinska Hospital, Stockholm, Sweden, f Department of Anatomy,
University of Cambridge, Cambridge, England, ** Department of Pharmacology, McGill
University, Montreal, Canada, t Laboratory of Molecular and Cellular Neuroscience,
Rockefeller University and # Department of Psychiatry, New York University Medical
Center, New York, New York
I. Introduction
Two systems are responsible for communication within higher organ­
isms, the endocrine system and the nervous system. Although distinct
differences between them are obvious, many similarities can also be
found. For example, during the last decades it has become increasingly
clear that they often share the same type of chemicals as messenger
molecules. Moreover, the endocrine and the nervous system are deeply
interconnected, and it is today difficult to approach neurobiological or
endocrinological problems without taking both systems into account.
Transmission of messages within the nervous system was long assumed
to occur via electrical events. In the beginning of this century, however,
the first experimental evidence was presented that chemical messengers
may be involved (Elliot, 1905). Elliott's studies were focused on the pe­
ripheral nervous system and implicated adrenaline as a possible transmit­
ter molecule. The demonstration of chemical transmission in the central
nervous system was achieved later. Thus, although this type of transmis­
sion was advocated by outstanding scientists (see Dale, 1935), it was not
until 1954 that the first unequivocal evidence for central chemical trans­
mission was presented in the form of acetylcholine mediating this function
in recurrent inhibition of Renshaw cells (see Eccles et ai, 1954).
1 The Gregory Pincus Memorial Lecture.
1
Copyright © 1986 by Academic Press, Inc.
All rights of reproduction in any form reserved.
2 TOMAS HÖKFELT ET AL.
Subsequently evidence from the biochemical studies of Vogt (1954)
suggested the possibility that noradrenaline may be a transmitter in the
central nervous system, a view that was strongly supported by histochem-
ical studies using the formaldehyde-induced fluorescence method of Falck
and Hillarp (Carlsson et al., 1962; Dahlström and Fuxe, 1964, 1965; Fuxe,
1965a,b). Also the noradrenaline precursor dopamine rapidly took a posi­
tion as transmitter candidate (Carlsson et al., 1958). In the next decade
attention was focused on amino acids including γ-aminobutyric acid
(GABA), glycine, and glutamate (see Fonnum, 1978).
Chemical messengers released from neurons was one of the basic ideas
developed by Ernst and Berta Scharrer and Bargmann in their description
of neurosecretory cells, which released their chemicals into the blood
stream (Bargmann and Scharrer, 1951; Scharrer and Scharrer, 1954).
Such neurosecretory neurons were present not only in the magnocellular
paraventricular and supraoptic nuclei projecting to the posterior pituitary,
but were also the types of neurons which subsequently were shown to
produce the messenger molecules involved in the control of anterior pitui­
tary hormone secretion, i.e., the hypothalamic-releasing and inhibitory
hormones transported in the portal vessels to the pituitary gland accord­
ing to the concept of Harris (1955).
The first identification of a neurosecretory product was achieved when
Du Vigneaud et al. (1954) succeeded in purifying and sequencing oxytocin
and vasopressin and showed them to be peptides consisting of nine amino
acids.
Peptides as messenger molecules received renewed interest, when
Guillemin, Schally, Vale, and their collaborators in a series of remarkable
achievements were able to demonstrate that the postulated hypothalamic
inhibitory and releasing hormones were peptides: thyrotropin-releasing
hormone (TRH) (Burgus et al., 1970; Nair et al., 1970), luteinizing hor­
mone-releasing hormone (LHRH) (Amoss et al., 1971; Schally et al.,
1971), somatostatin (Brazeau et al., 1973), corticotropin-releasing hor­
mone (CRF) (Spiess et al., 1981; Vale et al., 1981), and growth hormone-
releasing factor (GRF) (Brazeau et al., 1982; Guillemin et al., 1982; Rivier
et al., 1982; Spiess et ai, 1982, 1983; Bohlen et al., 1984). This develop­
ment has been covered in the program of the Laurentian Hormone Con­
ferences and is thoroughly documented in the series of Recent Progress in
Hormone Research (Van Dyke et al., 1955; Gréer, 1956; Guillemin, 1964,
1977; McCann and Ramirez, 1964; Barraclough, 1966; Martini et al., 1968;
Schally et al., 1968; Guai et al., 1972; Kastin et al., 1972; Reichlin et al.,
1972; Porter et al., 1973; Knobil, 1974, 1980; Yen et al., 1975; Vale et al.,
1975, 1983; Kaplan et al., 1976; Wilber et al., 1976; Labrie et al., 1978;
Krieger et al., 1980; Straus et al., 1981; Leeman et al., 1982; Guillemin et
al., 1984; Bloom et al., 1985; Gershengorn, 1985).
NEURONS WITH MULTIPLE MESSENGERS 3
The radioimmunological and immunohistochemical analysis with anti-
sera raised against these hypothalamic peptides revealed a surprisingly
wide distribution not only within hypothalamic nuclei outside the basal
hypothalamus, but also in extrahypothalamic areas including the spinal
cord and the peripheral nervous system (see Hökfelt et al, 1980a; Sny-
der, 1980; Krieger, 1983; books edited by Krieger et al, 1983; and
Björklund and Hökfelt, 1985). These findings raised the possibility that
such peptides, as well as several others, for example substance P (Otsuka
and Takahashi, 1977; Pernow, 1983), could have functions beyond those
of hypothalamic hormones, for example, as transmitters or modulators
(see Otsuka and Takahashi, 1977; Snyder, 1980; Pernow, 1983). The num­
ber of such peptide candidates has increased dramatically during the last
10 years. Moreover, it has been recognized that families of peptides exist
which arise sometimes from the same and sometimes from different genes
within the same cell. An example of this is the discovery of several sub­
stance P-like compounds belonging to the tachykinin family (Kimura et
al, 1983;Kangawaé?itf/., 1983; Minammo et ai, 1984; Nawa et al., 1983;
Tatemoto et al, 1986).
The abundance of peptides has raised the question of whether or not
they occur in separate systems, distinguished from the ones shown to
contain, for example, acetylcholine, noradrenaline, and 5-hydroxytrypt-
amine. This question is particularly relevant in the periphery, where a
large proportion of the neurons, e.g., in the sympathetic ganglia, have
long been positively identified as noradrenergic. In fact, the first evidence
for coexistence was observed in sympathetic ganglia, where noradrena-
line-containing cells could be demonstrated to contain somatostatin-like
immunoreactivity (Hökfelt et al, 1977a). Subsequently, it has been recog­
nized that coexistence situations embracing a classical transmitter and
peptide represent a common phenomenon and can be encountered both in
the peripheral and central nervous system. Moreover, in this search it has
been found that other types of coexistence situations occur, for example,
several peptides in a neuron without an identified classical transmitter, or
more than one classical transmitter.
The occurrence of multiple messengers in a cell has been known for a
long time. Thus, many endocrine cells in the gastointestinal tract have
been shown to contain both a peptide hormone and a biogenic amine, and
these cells have been regarded as belonging to a common system, the
APUD system (Pearse, 1969; Owman et al, 1973). Moreover, in inverte­
brates the coexistence of several transmitters was early observed (see
Osborne, 1983). More recently the adrenal medullary gland cells have
been shown to contain peptides, for example enkephalin-like peptides
(Fig. 1A-C) (Schultzberg et al, 1978a,b; Viveros et al., 1979; Lewis et
al, 1980, 1981; Stern et al, 1980), opening up possibilities of complex
4 TOMAS HÖKFELT ET AL.
c ENKi
iP»·1
FIG. 1. Immunofluorescence micrographs of the adrenal medulla after incubation with
antiserum to methionine-enkephalin (ENK) (A), phenylethanolamine-Ai-methyl transferase
(PNMT) (B), and dopamine /3-hydroxylase (DBH) (C). Strong ENK-like immunoreactivity
(ENK-LI) can be seen in an island o fcells (arrows in A), and these cells are PNMT negative
but strongly DBH positive. Thus, the ENK-LI is present in noradrenaline cells. Note ENK-
positive nerve endings. Bar indicates 50 μτη. From Schultzberg et al. (1978b).