Introduction: Injection of 3-iodothyronamine into experimental animals profoundly affects their metabolism and body temperature. As 3-iodothyronamine is rapidly acetylated in vivo after injection, it was hypothesized that the metabolites N- or O-acetyl-3-iodothyronamines could constitute the active hormones. Methods: Adult male mice were injected once daily with one of the metabolites (5 mg/kg body weight intraperitoneally dissolved in 60% DMSO in PBS) or solvent. Metabolism was monitored by indirect calorimetry, body temperature by infrared thermography, and body composition by nuclear magnetic resonance analysis. Signaling activities in brown fat or liver were assessed by studying target gene transcription by qPCR including uncoupling protein 1 or deiodinase type 1 or 2, and Western blot. Results: The markers of metabolism, body composition, or temperature tested were similar in the mice injected with solvent and those injected with one of the acetylated 3-iodothyronamines. Conclusions: In our experimental setup, N- and O-acetyl-3-iodothyronamine do not constitute compounds contributing to the metabolic or temperature effects described for 3-iodothyronamine. The acetylation of 3-iodothyronamine observed in vivo may thus rather serve degradation and elimination purposes.

1.
Köhrle
J
.
The Colorful Diversity of Thyroid Hormone Metabolites
.
Eur Thyroid J
.
2019
Jun
;
8
(
3
):
115
29
.
[PubMed]
2235-0640
2.
Köhrle
J
,
Biebermann
H
.
3-Iodothyronamine-A Thyroid Hormone Metabolite With Distinct Target Profiles and Mode of Action
.
Endocr Rev
.
2019
Apr
;
40
(
2
):
602
30
.
[PubMed]
0163-769X
3.
Scanlan
TS
,
Suchland
KL
,
Hart
ME
,
Chiellini
G
,
Huang
Y
,
Kruzich
PJ
, et al.
3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone
.
Nat Med
.
2004
Jun
;
10
(
6
):
638
42
.
[PubMed]
1078-8956
4.
Gachkar
S
,
Oelkrug
R
,
Martinez-Sanchez
N
,
Rial-Pensado
E
,
Warner
A
,
Hoefig
CS
, et al.
3-Iodothyronamine Induces Tail Vasodilation Through Central Action in Male Mice
.
Endocrinology
.
2017
Jun
;
158
(
6
):
1977
84
.
[PubMed]
0013-7227
5.
Galli
E
,
Marchini
M
,
Saba
A
,
Berti
S
,
Tonacchera
M
,
Vitti
P
, et al.
Detection of 3-iodothyronamine in human patients: a preliminary study
.
J Clin Endocrinol Metab
.
2012
Jan
;
97
(
1
):
E69
74
.
[PubMed]
0021-972X
6.
Hoefig
CS
,
Köhrle
J
,
Brabant
G
,
Dixit
K
,
Yap
B
,
Strasburger
CJ
, et al.
Evidence for extrathyroidal formation of 3-iodothyronamine in humans as provided by a novel monoclonal antibody-based chemiluminescent serum immunoassay
.
J Clin Endocrinol Metab
.
2011
Jun
;
96
(
6
):
1864
72
.
[PubMed]
0021-972X
7.
Saba
A
,
Chiellini
G
,
Frascarelli
S
,
Marchini
M
,
Ghelardoni
S
,
Raffaelli
A
, et al.
Tissue distribution and cardiac metabolism of 3-iodothyronamine
.
Endocrinology
.
2010
Oct
;
151
(
10
):
5063
73
.
[PubMed]
0013-7227
8.
Hackenmueller
SA
,
Scanlan
TS
.
Identification and quantification of 3-iodothyronamine metabolites in mouse serum using liquid chromatography-tandem mass spectrometry
.
J Chromatogr A
.
2012
Sep
;
1256
:
89
97
.
[PubMed]
0021-9673
9.
Harder
L
,
Schanze
N
,
Sarsenbayeva
A
,
Kugel
F
,
Köhrle
J
,
Schomburg
L
, et al.
In vivo Effects of Repeated Thyronamine Administration in Male C57BL/6J Mice
.
Eur Thyroid J
.
2018
Jan
;
7
(
1
):
3
12
.
[PubMed]
2235-0640
10.
Hoefig
CS
,
Jacobi
SF
,
Warner
A
,
Harder
L
,
Schanze
N
,
Vennström
B
, et al.
3-Iodothyroacetic acid lacks thermoregulatory and cardiovascular effects in vivo
.
Br J Pharmacol
.
2015
Jul
;
172
(
13
):
3426
33
.
[PubMed]
0007-1188
11.
Casero
RA
 Jr
,
Pegg
AE
.
Polyamine catabolism and disease
.
Biochem J
.
2009
Jul
;
421
(
3
):
323
38
.
[PubMed]
0264-6021
12.
Shen
Y
,
Tiralongo
J
,
Kohla
G
,
Schauer
R
.
Regulation of sialic acid O-acetylation in human colon mucosa
.
Biol Chem
.
2004
Feb
;
385
(
2
):
145
52
.
[PubMed]
1431-6730
13.
Warner
A
,
Rahman
A
,
Solsjö
P
,
Gottschling
K
,
Davis
B
,
Vennstrom
B
, et al.
Inappropriate heat dissipation ignites brown fat thermogenesis in mice with a mutant thyroid hormone receptor alpha 1.
Proceedings of the National Academy of Sciences of the United States of America
.
2013
14.
Johann
K
,
Cremer
AL
,
Fischer
AW
,
Heine
M
,
Pensado
ER
,
Resch
J
, et al.
Thyroid-Hormone-Induced Browning of White Adipose Tissue Does Not Contribute to Thermogenesis and Glucose Consumption.
Cell reports.
2019
Jun 11;27:3385-3400 e3383.
15.
Mittag
J
,
Behrends
T
,
Hoefig
CS
,
Vennström
B
,
Schomburg
L
.
Thyroid hormones regulate selenoprotein expression and selenium status in mice
.
PLoS One
.
2010
Sep
;
5
(
9
):
e12931
.
[PubMed]
1932-6203
16.
Hoefig
CS
,
Harder
L
,
Oelkrug
R
,
Meusel
M
,
Vennström
B
,
Brabant
G
, et al.
Thermoregulatory and Cardiovascular Consequences of a Transient Thyrotoxicosis and Recovery in Male Mice
.
Endocrinology
.
2016
Jul
;
157
(
7
):
2957
67
.
[PubMed]
0013-7227
17.
Braulke
LJ
,
Klingenspor
M
,
DeBarber
A
,
Tobias
SC
,
Grandy
DK
,
Scanlan
TS
, et al.
3-Iodothyronamine: a novel hormone controlling the balance between glucose and lipid utilisation
.
J Comp Physiol B
.
2008
Feb
;
178
(
2
):
167
77
.
[PubMed]
0174-1578
18.
Hackenmueller
SA
,
Marchini
M
,
Saba
A
,
Zucchi
R
,
Scanlan
TS
.
Biosynthesis of 3-iodothyronamine (T1AM) is dependent on the sodium-iodide symporter and thyroperoxidase but does not involve extrathyroidal metabolism of T4
.
Endocrinology
.
2012
Nov
;
153
(
11
):
5659
67
.
[PubMed]
0013-7227
19.
Hoefig
CS
,
Wuensch
T
,
Rijntjes
E
,
Lehmphul
I
,
Daniel
H
,
Schweizer
U
, et al.
Biosynthesis of 3-Iodothyronamine From T4 in Murine Intestinal Tissue
.
Endocrinology
.
2015
Nov
;
156
(
11
):
4356
64
.
[PubMed]
0013-7227
20.
Piehl
S
,
Hoefig
CS
,
Scanlan
TS
,
Köhrle
J
.
Thyronamines—past, present, and future
.
Endocr Rev
.
2011
Feb
;
32
(
1
):
64
80
.
[PubMed]
0163-769X
21.
Panas
HN
,
Lynch
LJ
,
Vallender
EJ
,
Xie
Z
,
Chen
GL
,
Lynn
SK
, et al.
Normal thermoregulatory responses to 3-iodothyronamine, trace amines and amphetamine-like psychostimulants in trace amine associated receptor 1 knockout mice
.
J Neurosci Res
.
2010
Jul
;
88
(
9
):
1962
9
.
[PubMed]
0360-4012
22.
Bräunig
J
,
Mergler
S
,
Jyrch
S
,
Hoefig
CS
,
Rosowski
M
,
Mittag
J
, et al.
3-Iodothyronamine Activates a Set of Membrane Proteins in Murine Hypothalamic Cell Lines
.
Front Endocrinol (Lausanne)
.
2018
Sep
;
9
:
523
.
[PubMed]
1664-2392
23.
Laurino
A
,
De Siena
G
,
Saba
A
,
Chiellini
G
,
Landucci
E
,
Zucchi
R
, et al.
In the brain of mice, 3-iodothyronamine (T1AM) is converted into 3-iodothyroacetic acid (TA1) and it is included within the signaling network connecting thyroid hormone metabolites with histamine
.
Eur J Pharmacol
.
2015
Aug
;
761
:
130
4
.
[PubMed]
0014-2999
24.
Schanze
N
,
Jacobi
SF
,
Rijntjes
E
,
Mergler
S
,
Del Olmo
M
,
Hoefig
CS
, et al.
3-Iodothyronamine Decreases Expression of Genes Involved in Iodide Metabolism in Mouse Thyroids and Inhibits Iodide Uptake in PCCL3 Thyrocytes
.
Thyroid
.
2017
Jan
;
27
(
1
):
11
22
.
[PubMed]
1050-7256
25.
Zhang
Y
,
Liu
Y
,
Walsh
M
,
Bokov
A
,
Ikeno
Y
,
Jang
YC
, et al.
Liver specific expression of Cu/ZnSOD extends the lifespan of Sod1 null mice
.
Mech Ageing Dev
.
2016
Mar
;
154
:
1
8
.
[PubMed]
0047-6374
26.
Schomburg
L
.
Selenium, selenoproteins and the thyroid gland: interactions in health and disease
.
Nat Rev Endocrinol
.
2011
Oct
;
8
(
3
):
160
71
.
[PubMed]
1759-5029
27.
Zucchi
R
,
Rutigliano
G
,
Saponaro
F
.
Novel thyroid hormones
.
Endocrine
.
2019
Oct
;
66
(
1
):
95
104
.
[PubMed]
1355-008X
28.
Sim
E
,
Abuhammad
A
,
Ryan
A
.
Arylamine N-acetyltransferases: from drug metabolism and pharmacogenetics to drug discovery
.
Br J Pharmacol
.
2014
Jun
;
171
(
11
):
2705
25
.
[PubMed]
0007-1188
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