Abstract
The hypothalamic-pituitary-adrenal (HPA) axis is central to homeostasis, stress responses, energy metabolism, and neuropsychiatric function. The history of this complex system involves discovery of the relevant glands (adrenal, pituitary, hypothalamus), hormones (cortisol, corticotropin, corticotropin-releasing hormone), and the receptors for these hormones. The adrenal and pituitary were identified by classical anatomists, but most of this history has taken place rather recently, and has involved complex chemistry, biochemistry, genetics, and clinical investigation. The integration of the HPA axis with modern neurology and psychiatry has cemented the role of endocrinology in contemporary studies of behavior.
References
1.
Else
T
, Auchus
RJ
, Miller
WL
. Adrenocortical carcinoma in a 17th-century girl
. J Steroid Biochem Mol Biol
. 2017
Jan
;165
Pt A
:109
–13
.
[PubMed]
0960-07602.
Morgagni
JB
. The seats and causes of diseases investigated by anatomy. (English translation by Benjamin Alexander)
. London
: A. Millar & T. Cadell
; 1769
.3.
Delle Piane
L
, Rinaudo
PF
, Miller
WL
. 150 years of congenital adrenal hyperplasia: translation and commentary of De Crecchio’s classic paper from 1865
. Endocrinology
. 2015
Apr
;156
(4
):1210
–7
.
[PubMed]
0013-72274.
Miller
WL
. A brief history of adrenal research: steroidogenesis - the soul of the adrenal
. Mol Cell Endocrinol
. 2013
May
;371
(1-2
):5
–14
.
[PubMed]
0303-72075.
Medvei
VC
. The History of Clinical Endocrinology: A Comprehensive Account of Endocrinology from Earliest Times to the Present Day
. Pearl River (NY)
: Parthenon Publishing Group
; 1993
. p. 77
. ISBN: 1-85070-427-9.6.
Rathke H Ueber die Entstehung der Glandula pituitaria. Archiv für Anatomie, Physiologie und wissenschaftliche Medicin.
1838
: 482-485 (https://biodiversitylibrary.org/page/14166635)7.
Vassale
G
, Sacchi
E
. Sulla distrutzione della ghiandola pituitaria.
Revista sperim. Di Freniatria 1893
, n.34. Arch Italien de Biologie (Torino) XVIII, fasc 3. p.385 (https://books.google.com/books?id=MoxIAQAAIAAJ)8.
Aschner
B
. Über die Funktion der Hypophyse.
Pflüger’s Arch Gesamm Physiol 1912
; 146:1–46. (ISSN: 0031-6768 (Print) 1432-2013 (Online)) 9.
Evans
HM
, Long
JA
. Characteristic effects upon growth, oestrus and ovulation induced by the intraperitoneal administration of fresh anterior hypophyseal substance
. Proc Natl Acad Sci USA
. 1922
Mar
;8
(3
):38
–9
.
[PubMed]
0027-842410.
Lindholm
J
. A century of pituitary surgery: schloffer’s legacy
. Neurosurgery
. 2007
Oct
;61
(4
):865
–7
.
[PubMed]
0148-396X11.
Cushing
H
. The pituitary body and its disorders
. Philadelphia, London
: Lippincott
; 1912
., http://books.google.com/books?id=oaMbAAAAIAAJ&oe=UTF-812.
Cushing
H
. Surgical experiences with pituitary disorders
. J Am Med Assn
. 1914
;63
:1515
–25
. 13.
Cushing
H.
The basophilic adenomas of the pituitary body and their clinical manifestations (pituitary basophilism). Bull Johns Hopkins Hosp 1932; 50:137–195. (BCI:BCI19330700005909). Reprinted in Obesity Research (now re-named Obesity) 1994
; 2:486-508. (DOI: )14.
Bishop
PM
, Close
HG
. A case of basophil adenoma of the anterior lobe of the pituitary: “Cushing’s syndrome”. Guy’s Hosp Rep 1932
; 82:143–153. (ISSN 0017-5889)15.
Albright
F
. Cushing’s syndrome: its pathology and physiology, its relationship to the adreno-genital syndrome, and its connection with the problem of the reaction of the body to injurious agents (“alarm reaction” of Selye)
. Harvey Lecture Series
. 1942–43
;1943
(38
):123
–86
.16.
Kepler
EJ
. Cushing’s disease; a primary disorder of the adrenal cortices?
Ann N Y Acad Sci
. 1949
Jun
;50
(6
Art. 6
):657
–78
.
[PubMed]
0077-892317.
Bauer
J
. The so-called Cushing’s Syndrome, its history, terminology and differential diagnosis
. Acta Med Scand
. 1950
;137
(6
):411
–6
.
[PubMed]
0001-610118.
Lindholm
J
. Cushing syndrome: Historical aspects. Pituitary 2000
; 3:97–104. (ISSN: 1386-341X (Print) 1573-7403 (Online))19.
Smith
PE
. Experimental ablation of the hypophysis in the frog embryo
. Science
. 1916
Aug
;44
(1130
):280
–2
.
[PubMed]
0036-807520.
Smith
PE
. The disabilities caused by hypophysectomy and their repair. The tuberal (hypothalamic) syndrome in the rat
. J Amer Med Assn
. 1927
;88
(3
):158
–61
. 21.
Smith
PE
. Hypopysectomy and replacement therapy in the rat
. Am J Anat
. 1930
;45
(2
):205
–73
. 0002-910622.
Magnus
R
, Shaffer
EA
. The action of pituitary extracts upon the kidney
. [Proceedings of the Physiological Society]
. J Physiol Suppl (Paris)
. 1902
;27
:ix
–x
. 0449-193923.
Bailey
P
, Bremer
F
. Experimental diabetes insipidus
. Arch Intern Med (Chic)
. 1921
;28
(6
):773
–803
. 0730-188X24.
Fisher
C
, Ingram
WR
, Hare
WK
, Ranson
SW
. The degeneration of the supraoptico-hypophyseal system in diabetes insipidus
. Anat Rec
. 1935
;63
(1
):29
–52
. 0003-276X25.
Ranson
SW
. Some functions of the hypothalamus: Harvey Lecture, December 17, 1936
. Bull N Y Acad Med
. 1937
May
;13
(5
):241
–71
.
[PubMed]
0028-709126.
Lieutaud
J
. Essais anatomiques contenant l’histoire exacte de toutes les parties qui composent le corps de l’homme avec la maniere de disséquer
. Paris
; 1742
.27.
Popa
GT
, Fielding
U
. Hypophysio-portal vessels and their colloid accompaniment
. J Anat
. 1933
Jan
;67
(Pt 2
):227
–232.1
.
[PubMed]
0021-878228.
Wislocki
GB
, King
LS
. The permeability of the hypophysis and hypothalamus to vital dyes, with a study of hypophyseal vascular supply
. Am J Anat
. 1936
;58
(2
):421
–72
. 0002-910629.
Green
JD
, Harris
GW
. The neurovascular link between the neurohypophysis and adenohypophysis. J Endocrinol. 1947
; 5: 136-146. (BCI:BCI19482200020656)30.
Harris
GW
. Neural control of the pituitary gland
. Physiol Rev
. 1948
Apr
;28
(2
):139
–79
.
[PubMed]
0031-933331.
Missaghian
E
, Kempná
P
, Dick
B
, Hirsch
A
, Alikhani-Koupaei
R
, Jégou
B
, et al. Role of DNA methylation in the tissue-specific expression of the CYP17A1 gene for steroidogenesis in rodents
. J Endocrinol
. 2009
Jul
;202
(1
):99
–109
.
[PubMed]
0022-079532.
Vogt
M
. The output of cortical hormone by the mammalian suprarenal
. J Physiol
. 1943
Dec
;102
(3
):341
–56
.
[PubMed]
0022-375133.
Osler
W
. Case of Addison’s disease – Death during treatment with the suprarenal extract. Johns Hopkins Hosp Bull 1896
; 7:208-209 (babel.hathitrust.org/cgi/pt?id=coo.31924069247371;view=1up;seq=270)34.
Simpson
SA
, Tait
JF
, Wettstein
A
, Neher
R
, Von Euw
J
, Reichstein
T
. Isolierung eines neuen kristallisierten Hormons aus Nebennieren mit besonders hoher Wirksamkeit auf den Mineralstoffwechsel
. Experientia
. 1953
Sep
;9
(9
):333
–5
.
[PubMed]
0014-475435.
Simpson
SA
, Tait
JF
, Wettstein
A
, Neher
R
, von Euw
J
, Schindler
O
, et al. Aldosteronisolierung und Eigenschaften über Bestandteile de Nebennierenrinde und verwandte Stoffe
. Helv Chim Acta
. 1954
;37
:1163
–200
. 0018-019X36.
Hechter
O
, Jacobsen
RP
, Jeanloz
RW
, Levy
H
, Pincus
G
, Schenker
V
. Pathways of corticosteroid synthesis. J Clin Endocrinol 1950
; 10: 827-828 (meeting abstract). ()37.
Hechter
O
, Pincus
G
. Genesis of the adrenocortical secretion
. Physiol Rev
. 1954
Jul
;34
(3
):459
–96
.
[PubMed]
0031-933338.
Miller
WL
, Auchus
RJ
. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders
. Endocr Rev
. 2011
Feb
;32
(1
):81
–151
.
[PubMed]
0163-769X39.
Kendall
EC
. Cortisone: Memoirs of a Hormone Hunter. New York: Charles Scribner's Sons, 1971
. pp175 (BCI:BCI197152077461)40.
Jacobsen
AW
, Koepf
GF
, Talbot
NB
, Wilkins
L
. Panel discussion, The adrenal gland in health and disease. Pediatrics 1949
3 515-548. Wilkins’ section is pp. 533-544. (http://pediatrics.aappublications.org/content/3/4/515)41.
Wilkins
L
, Lewis
RA
, Klein
R
, Rosemberg
E
. The suppression of androgen secretion by cortisone in a case of congenital adrenal hyperplasia
. [not on line]
. Bull Johns Hopkins Hosp
. 1950
Apr
;86
(4
):249
–52
.
[PubMed]
0097-138342.
Lewis
RA
, Wilkins
L
. The effect of the adrenocorticotrophic hormone in congenital adrenal hyperplasia with virilism and in Cushing’s syndrome treated with methyl testosterone
. J Clin Invest
. 1949
Mar
;28
(2
):394
–400
.
[PubMed]
0021-973843.
Bartter
FC
, Forbes
AO
, Leaf
A
. Congenital adrenal hyperplasia associated with the adrenogenital syndrome: An attempt to correct its disordered hormonal pattern. Journal of Clinical Investigation 1950
29 797 (abstract). (doi:.)44.
Wilkins
L
, Lewis
RA
, Klein
R
, Gardner
LI
, Crigler
JF
Jr, Rosemberg
E
, et al. Treatment of congenital adrenal hyperplasia with cortisone
. J Clin Endocrinol Metab
. 1951
Jan
;11
(1
):1
–25
.
[PubMed]
0021-972X45.
Bartter
FC
, Albright
F
, Forbes
AP
, Leaf
A
, Dempsey
E
, Carroll
E
. The effects of adrenocorticotropic hormone and cortisone in the adrenogenital syndrome associated with congenital adrenal hyperplasia: an attempt to explain and correct its disordered hormonal pattern
. J Clin Invest
. 1951
Mar
;30
(3
):237
–51
.
[PubMed]
0021-973846.
Ascoli
G
, Legani
T
. Die folgen der exstirpation der hypophyse
. Munch Med Wochenschr
. 1912
;59
:518
–21
.0027-297347.
Collip
JB
, Anderson
E
, Thomson
DL
. The adrenotropic hormone of the anterior pituitary lobe
. Lancet
. 1933
;222
(5737
):347
–8
. 0140-673648.
Simpson
ME
, Evans
HM
, Li
CH
. Bioassay of adrenocorticotropic hormone
. Endocrinology
. 1943
;33
(5
):261
–8
. 0013-722749.
Li
CH
, Evans
HM
, Simpson
ME
. Adrenocorticotrophic hormone
. J Biol Chem
. 1943
;149
:413
–24
. Available from: http://www.jbc.org/content/149/2/413.citation0021-925850.
Sayers
G
, White
A
, Long
CN
. Preparation and properties of pituitary adrenocorticotropic hormone
. J Biol Chem
. 1943
;149
:425
–36
. Available from: http://www.jbc.org/content/149/2/425.citation0021-925851.
Sayers
MA
, Sayers
G
, Woodbury
LA
. The assay of adrenocorticotrophic hormone by the adrenal ascorbic acid-depletion method
. Endocrinology
. 1948
May
;42
(5
):379
–93
.
[PubMed]
0013-722752.
Payne
RW
, Raben
MS
, Astwood
EB
. Extraction and purification of corticotropin
. J Biol Chem
. 1950
Dec
;187
(2
):719
–31
. Available from: http://www.jbc.org/content/187/2/719.citation
[PubMed]
0021-925853.
Stone
D
, Hechter
O
. Studies on ACTH action in perfused bovine adrenals: the site of action of ACTH in corticosteroidogenesis
. Arch Biochem Biophys
. 1954
Aug
;51
(2
):457
–69
.
[PubMed]
0003-986154.
Bell
PH
. Purification and structure of β-corticotrophin
. J Am Chem Soc
. 1954
;76
(21
):5565
–7
. 0002-786355.
Howard
KS
, Shepherd
RG
, Eigner
EA
, Davies
DS
, Bell
PH
. Structure of β-corticotrophin: final sequence
. J Am Chem Soc
. 1955
;77
(12
):3419
–20
. 0002-786356.
Shepherd
RG
, Howard
KS
, Bell
PH
, Cacciola
AR
, Child
RG
, Davies
MC
, et al. Studies with corticotropin. I. Isolation, purification and properties of β-corticotropin
. J Am Chem Soc
. 1956
;78
(19
):5051
–9
. 0002-786357.
Bell
PH
, Howard
KS
, Shepherd
RG
, Finn
BM
, Meisenhelder
JH
. Studies with corticotropin. II. Pepsin degradation of β –corticotropin
. J Am Chem Soc
. 1956
;78
(19
):5059
–66
. 0002-786358.
Shepherd
RG
, Willson
SD
, Howard
KS
, Bell
PH
, Davies
DS
, Davis
SB
, et al. Studies with corticotropin. III. Determination of the structure of β-corticotropin and its active degradation products
. J Am Chem Soc
. 1956
;78
(19
):5067
–76
. 0002-786359.
Li
CH
, Geschwind
II
, Dixon
JS
, Levy
AL
, Harris
JI
. Corticotropins (ACTH). I. Isolation of alpha-corticotropin from sheep pituitary glands
. J Biol Chem
. 1955
Mar
;213
(1
):171
–85
. Available from: http://www.jbc.org/content/213/1/171.citation
[PubMed]
0021-925860.
Li
CH
, Geschwind
II
, Cole
RD
, Raacke
ID
, Harris
JI
, Dixon
JS
. Amino-acid sequence of alpha-corticotropin
. Nature
. 1955
Oct
;176
(4484
):687
–9
.
[PubMed]
0028-083661.
Dixon
JS
, Li
CH
. Isolation and properties of corticotropin from bovine pituitary glands
. Science
. 1956
Nov
;124
(3228
):934
.
[PubMed]
0036-807562.
Liddle
GW
, Island
D
, Rinfret
AP
, Forsham
PH
. Factors enhancing the response of the human adrenal to corticotropin. Is there an adrenal growth factor?
J Clin Endocrinol Metab
. 1954
Aug
;14
(8
):839
–58
.
[PubMed]
0021-972X63.
Birk
Y
, Li
CH
. Isolation and properties of a new, biologically active peptide from sheep pituitary glands
. J Biol Chem
. 1964
Apr
;239
:1048
–52
. Available from: http://www.jbc.org/content/239/4/1048.citation
[PubMed]
0021-925864.
Chrétien
M
, Li
CH
. Isolation, purification, and characterization of gamma-lipotropic hormone from sheep pituitary glands
. Can J Biochem
. 1967
Jul
;45
(7
):1163
–74
.
[PubMed]
0008-401865.
Guillemin
R
, Vargo
T
, Rossier
J
, Minick
S
, Ling
N
, Rivier
C
, et al. beta-Endorphin and adrenocorticotropin are selected concomitantly by the pituitary gland
. Science
. 1977
Sep
;197
(4311
):1367
–9
.
[PubMed]
0036-807566.
Mains
RE
, Eipper
BA
, Ling
N
. Common precursor to corticotropins and endorphins
. Proc Natl Acad Sci USA
. 1977
Jul
;74
(7
):3014
–8
.
[PubMed]
0027-842467.
Roberts
JL
, Herbert
E
. Characterization of a common precursor to corticotropin and beta-lipotropin: cell-free synthesis of the precursor and identification of corticotropin peptides in the molecule
. Proc Natl Acad Sci USA
. 1977
Nov
;74
(11
):4826
–30
.
[PubMed]
0027-842468.
Roberts
JL
, Herbert
E
. Characterization of a common precursor to corticotropin and β-lipotropin: identification of β-lipotropin peptides and their arrangement relative to corticotropin in the precursor synthesized in a cell-free system
. Proc Natl Acad Sci USA
. 1977
;74
:5300
–4
.
[PubMed]
0027-842469.
Nakanishi
S
, Inoue
A
, Kita
T
, Nakamura
M
, Chang
AC
, Cohen
SN
, et al. Nucleotide sequence of cloned cDNA for bovine corticotropin-β-lipotropin precursor
. Nature
. 1979
Mar
;278
(5703
):423
–7
.
[PubMed]
0028-083670.
Estivariz
FE
, Iturriza
F
, McLean
C
, Hope
J
, Lowry
PJ
. Stimulation of adrenal mitogenesis by N-terminal proopiocortin peptides
. Nature
. 1982
Jun
;297
(5865
):419
–22
.
[PubMed]
0028-083671.
Ezkurdia
I
, Juan
D
, Rodriguez
JM
, Frankish
A
, Diekhans
M
, Harrow
J
, et al. Multiple evidence strands suggest that there may be as few as 19,000 human protein-coding genes
. Hum Mol Genet
. 2014
Nov
;23
(22
):5866
–78
.
[PubMed]
0964-690672.
Wade
N
. The Nobel Duel - Two Scientists’ 21-year Race to Win the World’s Most Coveted Research Prize
. Garden City (NY)
: Anchor Press/Doubleday
; 1981
.ISBN: 978-0385149815.73.
Guillemin
R
, Rosenberg
B
. Humoral hypothalamic control of anterior pituitary: a study with combined tissue cultures
. Endocrinology
. 1955
Nov
;57
(5
):599
–607
.
[PubMed]
0013-722774.
Saffran
M
, Schally
AV
. The release of corticotrophin by anterior pituitary tissue in vitro
. Can J Biochem Physiol
. 1955
May
;33
(3
):408
–15
.
[PubMed]
0576-554475.
Vale
W
, Spiess
J
, Rivier
C
, Rivier
J
. Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin
. Science
. 1981
Sep
;213
(4514
):1394
–7
.
[PubMed]
0036-807576.
Furutani
Y
, Morimoto
Y
, Shibahara
S
, Noda
M
, Takahashi
H
, Hirose
T
, et al. Cloning and sequence analysis of cDNA for ovine corticotropin-releasing factor precursor
. Nature
. 1983
Feb
;301
(5900
):537
–40
.
[PubMed]
0028-083677.
Swanson
LW
, Sawchenko
PE
, Rivier
J
, Vale
WW
. Organization of ovine corticotropin-releasing factor immunoreactive cells and fibers in the rat brain: an immunohistochemical study
. Neuroendocrinology
. 1983
;36
(3
):165
–86
.
[PubMed]
0028-383578.
Rivier
C
, Rivier
J
, Vale
W
. Stress-induced inhibition of reproductive functions: role of endogenous corticotropin-releasing factor
. Science
. 1986
Feb
;231
(4738
):607
–9
.
[PubMed]
0036-807579.
Sapolsky
R
, Rivier
C
, Yamamoto
G
, Plotsky
P
, Vale
W
. Interleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor
. Science
. 1987
Oct
;238
(4826
):522
–4
.
[PubMed]
0036-807580.
Stenzel-Poore
MP
, Heinrichs
SC
, Rivest
S
, Koob
GF
, Vale
WW
. Overproduction of corticotropin-releasing factor in transgenic mice: a genetic model of anxiogenic behavior
. J Neurosci
. 1994
May
;14
(5 Pt 1
):2579
–84
. Available from: http://www.jneurosci.org/content/14/5/2579
[PubMed]
0270-647481.
Gillies
GE
, Linton
EA
, Lowry
PJ
. Corticotropin releasing activity of the new CRF is potentiated several times by vasopressin
. Nature
. 1982
Sep
;299
(5881
):355
–7
.
[PubMed]
0028-083682.
Butcher
RW
, Sutherland
EW
. Adenosine 3′,5′-phosphate in biological materials. I. Purification and properties of cyclic 3′,5′-nucleotide phosphodiesterase and use of this enzyme to characterize adenosine 3′,5′-phosphate in human urine
. J Biol Chem
. 1962
Apr
;237
:1244
–50
. Available from: http://www.jbc.org/content/237/4/1244.citation
[PubMed]
0021-925883.
Robison
GA
, Butcher
RW
, Sutherland
EW
. Cyclic AMP
. Annu Rev Biochem
. 1968
;37
(1
):149
–74
.
[PubMed]
0066-415484.
Jensen
EV
, Jacobson
HI
. Basic guides to the mechanism of estrogen action.
Recent Prog Horm Res 1962
; 18: 387-414. (BCI:BCI19624000014473)85.
Ashburner
M
. Sequential gene activation by ecdysone in polytene chromosomes of Drosophila melanogaster: I. Dependence upon ecdysone concentration
. Dev Biol
. 1974
;39
(1
):141
–57
.
[PubMed]
0012-160686.
O’Malley
BW
, McGuire
WL
, Kohler
PO
, Korenman
SG
. Studies on the mechanism of steroid hormone regulation of synthesis of specific proteins.
Recent Prog Horm Res 1969
; 25: 105-160. (ISBN: 9781483219462) 87.
O’Malley
BW
, Means
AR
. Female steroid hormones and target cell nuclei
. Science
. 1974
Feb
;183
(4125
):610
–20
.
[PubMed]
0036-807588.
Rousseau
G
, Baxter
JD
, Funder
JW
, Edelman
IS
, Tomkins
GM
. Glucocorticoid and mineralocorticoid receptors for aldosterone
. J Steroid Biochem
. 1972
Feb
;3
(2
):219
–27
.
[PubMed]
0022-473189.
Hollenberg
SM
, Weinberger
C
, Ong
ES
, Cerelli
G
, Oro
A
, Lebo
R
, et al. Primary structure and expression of a functional human glucocorticoid receptor cDNA
. Nature
. 1985
Dec
;318
(6047
):635
–41
.
[PubMed]
0028-083690.
Miesfeld
R
, Rusconi
S
, Godowski
PJ
, Maler
BA
, Okret
S
, Wikström
AC
, et al. Genetic complementation of a glucocorticoid receptor deficiency by expression of cloned receptor cDNA
. Cell
. 1986
Aug
;46
(3
):389
–99
.
[PubMed]
0092-867491.
Green
S
, Walter
P
, Kumar
V
, Krust
A
, Bornert
JM
, Argos
P
, et al. Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A
. Nature
. 1986
Mar
;320
(6058
):134
–9
.
[PubMed]
0028-083692.
Evans
RM
. The steroid and thyroid hormone receptor superfamily
. Science
. 1988
May
;240
(4854
):889
–95
.
[PubMed]
0036-807593.
Yamamoto
KR
. Steroid receptor regulated transcription of specific genes and gene networks
. Annu Rev Genet
. 1985
;19
(1
):209
–52
.
[PubMed]
0066-419794.
Arriza
JL
, Weinberger
C
, Cerelli
G
, Glaser
TM
, Handelin
BL
, Housman
DE
, et al. Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor
. Science
. 1987
Jul
;237
(4812
):268
–75
.
[PubMed]
0036-807595.
Funder
JW
, Pearce
PT
, Smith
R
, Smith
AI
. Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated
. Science
. 1988
Oct
;242
(4878
):583
–5
.
[PubMed]
0036-807596.
Edwards
CR
, Stewart
PM
, Burt
D
, Brett
L
, McIntyre
MA
, Sutanto
WS
, et al. Localisation of 11 beta-hydroxysteroid dehydrogenase—tissue specific protector of the mineralocorticoid receptor
. Lancet
. 1988
Oct
;2
(8618
):986
–9
.
[PubMed]
0140-673697.
Benediktsson
R
, Calder
AA
, Edwards
CR
, Seckl
JR
. Placental 11 beta-hydroxysteroid dehydrogenase: a key regulator of fetal glucocorticoid exposure
. Clin Endocrinol (Oxf)
. 1997
Feb
;46
(2
):161
–6
.
[PubMed]
0300-066498.
Tomlinson
JW
, Walker
EA
, Bujalska
IJ
, Draper
N
, Lavery
GG
, Cooper
MS
, et al. 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response
. Endocr Rev
. 2004
Oct
;25
(5
):831
–66
.
[PubMed]
0163-769X99.
Welberg
LA
, Seckl
JR
. Prenatal stress, glucocorticoids and the programming of the brain
. J Neuroendocrinol
. 2001
Feb
;13
(2
):113
–28
.
[PubMed]
0953-8194100.
Liu
D
, Diorio
J
, Tannenbaum
B
, Caldji
C
, Francis
D
, Freedman
A
, et al. Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress
. Science
. 1997
Sep
;277
(5332
):1659
–62
.
[PubMed]
0036-8075101.
Weaver
IC
, Cervoni
N
, Champagne
FA
, D’Alessio
AC
, Sharma
S
, Seckl
JR
, et al. Epigenetic programming by maternal behavior
. Nat Neurosci
. 2004
Aug
;7
(8
):847
–54
.
[PubMed]
1097-6256102.
Lupien
SJ
, McEwen
BS
, Gunnar
MR
, Heim
C
. Effects of stress throughout the lifespan on the brain, behaviour and cognition
. Nat Rev Neurosci
. 2009
Jun
;10
(6
):434
–45
.
[PubMed]
1471-003X103.
Evanson
NK
, Herman
JP
, Sakai
RR
, Krause
EG
. Nongenomic actions of adrenal steroids in the central nervous system
. J Neuroendocrinol
. 2010
Aug
;22
(8
):846
–61
.
[PubMed]
1365-2826104.
Lefkowitz
RJ
, Roth
J
, Pricer
W
, Pastan
I
. ACTH receptors in the adrenal: specific binding of ACTH-125I and its relation to adenyl cyclase
. Proc Natl Acad Sci USA
. 1970
Mar
;65
(3
):745
–52
.
[PubMed]
0027-8424105.
Buckley
DI
, Ramachandran
J
. Characterization of corticotropin receptors on adrenocortical cells
. Proc Natl Acad Sci USA
. 1981
Dec
;78
(12
):7431
–5
.
[PubMed]
0027-8424106.
Mountjoy
KG
, Robbins
LS
, Mortrud
MT
, Cone
RD
. The cloning of a family of genes that encode the melanocortin receptors
. Science
. 1992
Aug
;257
(5074
):1248
–51
.
[PubMed]
0036-8075107.
Roselli-Rehfuss
L
, Mountjoy
KG
, Robbins
LS
, Mortrud
MT
, Low
MJ
, Tatro
JB
, et al. Identification of a receptor for gamma melanotropin and other proopiomelanocortin peptides in the hypothalamus and limbic system
. Proc Natl Acad Sci USA
. 1993
Oct
;90
(19
):8856
–60
.
[PubMed]
0027-8424108.
Gantz
I
, Konda
Y
, Tashiro
T
, Shimoto
Y
, Miwa
H
, Munzert
G
, et al. Molecular cloning of a novel melanocortin receptor
. J Biol Chem
. 1993
Apr
;268
(11
):8246
–50
. Available from: http://www.jbc.org/content/268/11/8246
[PubMed]
0021-9258109.
Gantz
I
, Miwa
H
, Konda
Y
, Shimoto
Y
, Tashiro
T
, Watson
SJ
, et al. Molecular cloning, expression, and gene localization of a fourth melanocortin receptor
. J Biol Chem
. 1993
Jul
;268
(20
):15174
–9
. Available from: http://www.jbc.org/content/268/20/15174
[PubMed]
0021-9258110.
Mountjoy
KG
, Mortrud
MT
, Low
MJ
, Simerly
RB
, Cone
RD
. Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain
. Mol Endocrinol
. 1994
Oct
;8
(10
):1298
–308
.
[PubMed]
0888-8809111.
Chen
W
, Kelly
MA
, Opitz-Araya
X
, Thomas
RE
, Low
MJ
, Cone
RD
. Exocrine gland dysfunction in MC5-R-deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides
. Cell
. 1997
Dec
;91
(6
):789
–98
.
[PubMed]
0092-8674112.
Jackson
DS
, Ramachandrappa
S
, Clark
AJ
, Chan
LF
. Melanocortin receptor accessory proteins in adrenal disease and obesity
. Front Neurosci
. 2015
Jun
;9
:213
.
[PubMed]
1662-4548113.
Metherell
LA
, Chapple
JP
, Cooray
S
, David
A
, Becker
C
, Rüschendorf
F
, et al. Mutations in MRAP, encoding a new interacting partner of the ACTH receptor, cause familial glucocorticoid deficiency type 2
. Nat Genet
. 2005
Feb
;37
(2
):166
–70
.
[PubMed]
1061-4036114.
Cone
RD
. Anatomy and regulation of the central melanocortin system
. Nat Neurosci
. 2005
May
;8
(5
):571
–8
.
[PubMed]
1097-6256115.
De Souza
EB
, Insel
TR
, Perrin
MH
, Rivier
J
, Vale
WW
, Kuhar
MJ
. Corticotropin-releasing factor receptors are widely distributed within the rat central nervous system: an autoradiographic study
. J Neurosci
. 1985
Dec
;5
(12
):3189
–203
. Available from: http://www.jneurosci.org/content/5/12/3189
[PubMed]
0270-6474116.
De Souza
EB
, Whitehouse
PJ
, Kuhar
MJ
, Price
DL
, Vale
WW
. Reciprocal changes in corticotropin-releasing factor (CRF)-like immunoreactivity and CRF receptors in cerebral cortex of Alzheimer’s disease
. Nature
. 1986
Feb
;319
(6054
):593
–5
.
[PubMed]
0028-0836117.
Perrin
MH
, Haas
Y
, Rivier
JE
, Vale
WW
. Corticotropin-releasing factor binding to the anterior pituitary receptor is modulated by divalent cations and guanyl nucleotides
. Endocrinology
. 1986
Mar
;118
(3
):1171
–9
.
[PubMed]
0013-7227118.
Chen
R
, Lewis
KA
, Perrin
MH
, Vale
WW
. Expression cloning of a human corticotropin-releasing-factor receptor
. Proc Natl Acad Sci USA
. 1993
Oct
;90
(19
):8967
–71
.
[PubMed]
0027-8424119.
Bale
TL
, Vale
WW
. CRF and CRF receptors: role in stress responsivity and other behaviors
. Annu Rev Pharmacol Toxicol
. 2004
;44
(1
):525
–57
.
[PubMed]
0362-1642120.
Bale
TL
, Contarino
A
, Smith
GW
, Chan
R
, Gold
LH
, Sawchenko
PE
, et al. Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress
. Nat Genet
. 2000
Apr
;24
(4
):410
–4
.
[PubMed]
1061-4036121.
Selye
H
. A syndrome produced by diverse nocuous agents
. Nature
. 1936
;138
(3479
):32
. 0028-0836122.
Selye
H
. The general adaptation syndrome and the diseases of adaptation
. J Clin Endocrinol Metab
. 1946
Feb
;6
(2
):117
–230
.
[PubMed]
0021-972X123.
Selye
H
. Anesthetic effect of steroid hormones
. Proc Soc Exp Biol Med
. 1941
;46
(1
):116
–21
. Available from: journals.sagepub.com/doi/abs/10.3181/00379727-46-119070037-9727124.
Compagnone
NA
, Mellon
SH
. Neurosteroids: biosynthesis and function of these novel neuromodulators
. Front Neuroendocrinol
. 2000
Jan
;21
(1
):1
–56
.
[PubMed]
0091-3022125.
Liddle
GW
, Island
D
, Lance
EM
, Harris
AP
. Alterations of adrenal steroid patterns in man resulting from treatment with a chemical inhibitor of 11 beta-hydroxylation
. J Clin Endocrinol Metab
. 1958
Aug
;18
(8
):906
–12
.
[PubMed]
0021-972X126.
Liddle
GW
, Estep
HL
, Kendall
JW
Jr, Williams
WC
Jr, Townes
AW
. Clinical application of a new test of pituitary reserve
. J Clin Endocrinol Metab
. 1959
Aug
;19
(8
):875
–94
.
[PubMed]
0021-972X127.
Liddle
GW
. Tests of pituitary-adrenal suppressibility in the diagnosis of Cushing’s syndrome
. J Clin Endocrinol Metab
. 1960
Dec
;20
(12
):1539
–60
.
[PubMed]
0021-972X128.
Meador
CK
, Liddle
GW
, Island
DP
, Nicholson
WE
, Lucas
CP
, Nuckton
JG
, et al. Cause of Cushing’s syndrome in patients with tumors arising from “nonendocrine” tissue
. J Clin Endocrinol Metab
. 1962
Jul
;22
(7
):693
–703
.
[PubMed]
0021-972X129.
Dexter
RN
, Fishman
LM
, Ney
RL
, Liddle
GW
. Inhibition of adrenal corticosteroid synthesis by aminoglutethimide: studies of the mechanism of action
. J Clin Endocrinol Metab
. 1967
Apr
;27
(4
):473
–80
.
[PubMed]
0021-972X130.
Fishman
LM
, Liddle
GW
, Island
DP
, Fleischer
N
, Küchel
O
. Effects of amino-glutethimide on adrenal function in man
. J Clin Endocrinol Metab
. 1967
Apr
;27
(4
):481
–90
.
[PubMed]
0021-972X131.
Gold
PW
, Loriaux
DL
, Roy
A
, Kling
MA
, Calabrese
JR
, Kellner
CH
, et al. Responses to corticotropin-releasing hormone in the hypercortisolism of depression and Cushing’s disease. Pathophysiologic and diagnostic implications
. N Engl J Med
. 1986
May
;314
(21
):1329
–35
.
[PubMed]
0028-4793132.
Chrousos
GP
, Gold
PW
. The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis
. JAMA
. 1992
Mar
;267
(9
):1244
–52
.
[PubMed]
0098-7484133.
Gold
PW
, Chrousos
GP
. Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. Mol Psych 7254-275, 2002
. (DOI: )134.
Miller
WL
. Steroidogenesis: unanswered Questions
. Trends Endocrinol Metab
. 2017
Nov
;28
(11
):771
–93
.
[PubMed]
1043-2760© 2018 S. Karger AG, Basel
2018
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