Tshr

Thyrotropin receptor (Thyroid-stimulating hormone receptor) (TSH-R)

Spatial tier: STRICT_EXCLUSIVE · Class: GPCR · Top region: ME (Median eminence) · Positive regions: 9/554

47.1Discovery Score
43.2Targetability Score
CEvidence grade C
What this means: Tshr: predicted fine-region profile is strict-exclusive, with 9 positive regions out of 554 (limit 12); direct spatial validation is required.

Function in ME: evidence, prediction, innovation

Gene function
Tshr encodes the thyroid-stimulating hormone receptor, a leucine-rich-repeat class-A GPCR with a large hormone-binding ectodomain. TSH binding activates Gs-cAMP-PKA and, at higher occupancy, Gq-PLC. Outside the thyroid, TSHR on hypothalamic tanycytes reads TSH released locally from the pituitary pars tuberalis.
Region function
The median eminence and adjacent pars tuberalis form the neurohaemal hub where tanycytes, portal capillaries and neurosecretory terminals meet; tanycytes locally convert thyroid hormone and gate GnRH and TRH access to portal blood.
Published in this region
direct Direct and well developed. Ono et al. 2008 (PNAS) showed long photoperiod induces pars tuberalis Tshb and that TSH acting on TSHR in the mediobasal hypothalamus/median eminence induces Dio2 and suppresses Dio3, raising local T3. Bolborea et al. 2015 (J Mol Endocrinol) showed tanycyte TSHR signals via both cAMP and Ca2+/PKC. Kameda 2023 (J Comp Neurol) documented photoperiod-dependent tanycyte and pars tuberalis changes; Rodriguez-Rodriguez et al. 2019 reviewed tanycyte control of TRH flux into portal capillaries.
Predicted function
Prediction: TSHR converts the melatonin-decoded photoperiod signal into intra-hypothalamic T3 by switching the tanycyte Dio2/Dio3 balance, remodelling end-feet around GnRH terminals and gating seasonality. Tanycyte-selective Tshr deletion should abolish long-day Dio2 induction and block photoperiodic gonadal activation; local TSH infusion or tanycyte Gs-DREADD activation should mimic a summer state with raised T3 and gonadal recrudescence.
Innovation
★☆☆☆☆ 1/5 TSHR signalling in tanycytes of the median eminence is the textbook mechanism of mammalian photoperiodism and has been studied for nearly two decades.
Tools
Tshr knockout and hyt/hyt mice; floxed Tshr alleles; tanycyte drivers Rax-CreERT2 and Dio2/Gpr50 promoters with ICV AAV1; recombinant bovine TSH for ICV infusion; anti-TSHR antibodies; TSHR small-molecule agonists/antagonists.
References

Direct evidence located at the region

Tshr Allen ISH at the CCF centroid of ME

Allen ISH experiment 80471957, section image 80444872 (section 144): the section that contains the CCF centroid of Median eminence according to the Allen image-to-atlas alignment (reference_to_image), with a 2 mm window around that point. Left: whole section, red box = window. Middle: ISH signal. Right: Allen's expression-mask view of the same window. open this image in the Allen viewer

Direct spatial evidence

MERFISH REGION LOCATOR
ME MERFISH region locator
Real single-cell MERFISH coordinates for the ME (Median eminence) section -- our own ground-truth data, showing exactly where this region sits, independent of whether the Allen ISH section below is easy to read.
DIRECT ALLEN ISH
Allen ISH experiment 80471957, image 80444828 -- target region: ME (Median eminence)
Allen ISH experiment 80471957, image 80444828 -- target region: ME (Median eminence)
DIRECT ALLEN ISH
Allen ISH experiment 80471957, image 80444830 -- target region: ME (Median eminence)
Allen ISH experiment 80471957, image 80444830 -- target region: ME (Median eminence)

Regional expression figure

Tshr regional expression profile

Predicted WMB × fine-CCF profile; not direct full-transcriptome spatial measurement.

Spatial profile

ME
2.65
OV
2.62
PVi
1.25
ARH
1.13
PVp
0.941
DTN
0.915
MA
0.835
NDB
0.697
MS
0.691
SFO
0.643
AP
0.544
PAS
0.526
IPI
0.511
OT
0.492
IPA
0.458
LC
0.454
AAA
0.453
AVPV
0.434
CU
0.393
SI
0.389

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.387
Top-region fraction
0.124
Filter status
PASS

Interpretation limits