Endocrine and hormone signaling

The endocrine system couples hormones (steroids, amino-acid derivatives, peptides/proteins) to target receptors, governing metabolism, growth, reproduction, stress, and electrolyte balance. Nuclear receptors drive genomic programs; membrane receptors (RTKs, GPCRs, etc.) initiate kinase cascades that intersect metabolism, immunity, and hormone-dependent cancer phenotypes.

1. Key targets

Nuclear receptors & sex-hormone axis

  • ESR1 / ESR2

    Estrogen receptors; proliferation/transcription programs in breast, uterus, etc.—core to endocrine therapy and resistance.

  • AR

    Androgen receptor; prostate and subset breast contexts—splice variants (AR-Vs) link to resistance.

  • PGR / NR3C1

    Progesterone and glucocorticoid receptors—reproductive cycling, stress responses, immune–metabolic coupling.

Metabolic & growth axes (membrane receptors)

  • INSR、IGF1R、IRS1/2
  • GH–IGF1 axis: GHR, JAK2/STAT5 downstream
  • Extensive crosstalk with PI3K/Akt, mTOR, MAPK

Thyroid & hypothalamic–pituitary

  • TSHR、THRA/THRB（甲状腺激素核受体）
  • TRH, TSH, GnRH, FSH/LH, PRL—peptide hormones and cognate GPCR/glycoprotein receptors

Supplement: endocrine & hormone targets (gene symbols)

Below the overview above, HGNC symbols are grouped by nuclear receptors, steroidogenesis, thyroid–parathyroid, hypothalamic–pituitary, metabolic/adipokine, reproduction/lactation, catecholamines, membrane receptors, carriers/transporters, and melatonin/circadian modules, plus selected immunometabolic crosstalk. Mind splice isoforms and paralogs—annotate with HGNC/UniProt.

Nuclear receptors

Nuclear receptor superfamily (major members)

Ligands include steroids, thyroid/retinoid/vitamin D, bile acids, oxysterols; mind splice isoforms and tissue bias.

NR0B1, NR0B2, THRA, THRB, RARA, RARB, RARG, RXRA, RXRB, RXRG, PPARA, PPARD, PPARG, NR1D1, NR1D2, NR1H2, NR1H3, NR1H4, NR1I2, NR1I3, VDR, RORA, RORB, RORC, HNF4A, HNF4G, NR2C1, NR2C2, NR2E1, NR2E3, NR2F1, NR2F2, NR2F6, ESR1, ESR2, ESRRG, ESRRB, ESRRA, PGR, AR, NR3C1, NR3C2, NR4A1, NR4A2, NR4A3, NR5A1, NR5A2, NR6A1

Steroidogenesis & steroid metabolism

Thyroid, parathyroid & calcium homeostasis

Thyroid axis (hormones, receptors, transport, deiodinases)

TG, TPO, TSHB, TSHR, SLC5A5, SLC16A2, THRA, THRB, DIO1, DIO2, DIO3, IYD, DUOX1, DUOX2

PTH, calcitonin & calcium sensing

PTH, PTHLH, PTH1R, PTH2R, CALCA, CALCB, CALCR, CALCRL, RAMP1, RAMP2, RAMP3, CASR, GCM2

Hypothalamic–pituitary hormones

Hypothalamic releasing / inhibitory hormones & related peptides

GNRH1, CRH, TRH, SST, GHRH, POMC, NPY, AGRP, CARTPT, KISS1, TAC1, TAC3, HCRT, PDYN, PENK, PMCH

Anterior / intermediate pituitary hormones & subunits

GH1, GH2, PRL, TSHB, LHB, FSHB, CGA, POMC, CSH1, CSH2

Neurohypophyseal hormones

AVP, OXT

Metabolic hormones & adipokines

Insulin–glucagon–incretin axis

INS, IGF1, IGF2, INSR, IGF1R, INSRR, IRS1, IRS2, IRS4, GCG, GIP, GIPR, GLP1R, GLP2R, GCGR, PCSK1, PCSK2, FURIN

Adipokines & energy-sensing endocrine crosstalk

LEP, LEPR, ADIPOQ, ADIPOR1, ADIPOR2, RETN, RBP4, NAMPT, FGF21, FGF19, FGFR4, KLB, FGFR1

Reproductive axis & lactation

Reproductive axis (hormones & membrane receptors, selected)

INHA, INHBA, INHBB, INHBC, AMH, AMHR2, BMP15, GDF9, ESR1, ESR2, PGR, AR

Lactation & GH-axis coupling

PRL, PRLR, GH1, GH2, GHR, JAK2, STAT5A, STAT5B, STAT3, IGF1, IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, IGFBP6, IGFBP7

Adrenal medulla & catecholamines

Adrenal medulla catecholamine synthesis & turnover

TH, DDC, DBH, PNMT, COMT, MAOA, MAOB, SLC6A2, SLC6A3, SLC6A4, ADRA1A, ADRA1B, ADRA1D, ADRA2A, ADRA2B, ADRA2C, ADRB1, ADRB2, ADRB3, DRD1, DRD2, DRD3, DRD4, DRD5

Membrane receptors (glycoprotein hormones, GPCRs, etc.)

Glycoprotein-hormone receptors & related GPCRs

TSHR, FSHR, LHCGR, GNRHR, TRHR, CRHR1, CRHR2, GHRHR, SSTR1, SSTR2, SSTR3, SSTR4, SSTR5, AVPR1A, AVPR1B, AVPR2, OXTR, MC1R, MC2R, MC3R, MC4R, MC5R, KISS1R, GHSR, MLNR, RXFP1, RXFP2, RXFP3, RXFP4

Additional peptide-hormone membrane receptors (selected)

PTH1R, PTH2R, CALCR, CALCRL, GLP1R, GLP2R, GIPR, GCGR, VIPR1, VIPR2, ADCYAP1R1, SCTR, NPY1R, NPY2R, NPY4R, NPY5R, AGTR1, AGTR2, BDKRB1, BDKRB2, EDNRA, EDNRB

Binding proteins & transporters

Hormone-binding proteins & carriers

SHBG, SERPINA6, ALB, IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, IGFBP6, IGFBP7, GC, SERPINA7

Transporters for hormones & metabolites (selected)

SLC2A1, SLC2A2, SLC2A3, SLC2A4, SLC16A1, SLC16A2, SLC16A7, SLC16A8, SLCO1A2, SLCO1B1, SLCO1B3, SLCO2B1, ABCB1, ABCG2

Melatonin & circadian clock

Melatonin receptors & biosynthetic enzymes

MTNR1A, MTNR1B, AANAT, ASMT

Circadian–nuclear receptor crosstalk (selected)

CLOCK, ARNTL, NPAS2, PER1, PER2, PER3, CRY1, CRY2, NR1D1, NR1D2, RORA, RORB, RORC

2. Suggested experimental readouts

For nuclear receptors, consider subcellular localization, cofactors, and chromatin context; pair phospho readouts with stimulation/antagonism and total protein controls.

  • Nuclear translocation of ERα/AR/PGR/NR3C1 and target genes (TFF1, KLK3, GRE reporters—model-dependent)
  • INSR/IGF1R and IRS1 Tyr phosphorylation; Akt, S6K, 4E-BP1 (mTOR pairing)
  • STAT5 (PRL/GH axis), STAT3 (context-dependent)
  • Thyroid hormone response genes (e.g., DIO2, UCP) and THRA/THRB isoform expression
  • Steroidogenic enzymes (CYP11A1, HSD3B, etc.) and adrenal/gonadal IHC

3. Nuclear receptors vs membrane hormone signaling

Hormone class (examples)Primary receptorsInitial signalNotes
Steroids (estrogen/progestin/androgen/glucocorticoid)ESR / PGR / AR / NR3C1…Ligand–receptor nuclear transcriptional programsSlower kinetics; cofactors and chromatin accessibility matter.
Peptide/protein (insulin, IGF, GH)INSR、IGF1R、GHR…RTK → IRS / JAK–STAT…Rapid coupling to metabolism/translation; mind species & culture conditions.
Hypothalamic releasing factors, catecholamines, etc.GPCR 家族G 蛋白 → AC / PLC / β-arrestin…Crosses Ca²⁺, cAMP, MAPK; initiates pituitary secretory cascades.

4. Clinical & drug context (illustrative)

  • Hormone-dependent cancers: ER/PR in breast cancer and AR in prostate cancer anchor stratification and first-line endocrine therapy—interpret with mutations, co-expression, and TME.
  • Metabolic syndrome & diabetes: Insulin resistance and IGF axis couple to obesity-associated inflammation—often studied with PI3K/Akt/mTOR.
  • Thyroid & autoimmunity: TSHR antibodies vs replacement vs antithyroid drugs differ mechanistically—annotate hyper- vs hypothyroid models.

Endocrine and hormone–related antibodies (curated)

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5. Product lines & on-site search

Primary & phospho antibodies

ERα/ERβ, PR, AR, NR3C1, INSR, IGF1R, IRS1, STAT5, TSHR, thyroglobulin/TPO—WB/IHC/IF/FC per datasheet and specimen type.

Recombinant proteins / standards

Insulin, IGF1, GH, receptor ECD/Fc fusions (availability-dependent) for binding or neutralization assays.

ELISA / multiplex

Insulin, C-peptide, cortisol, SHBG, etc.—follow ethics and biosafety.

6. Inhibitors & tool compounds (summary)

For research use; clinical drugs in cellular models require concentration/specificity controls per datasheets and literature.

Tamoxifen / 4-OHT

SERM; 4-OHT common in vitro.

Fulvestrant

SERD / ER degrader—resistance and combination studies.

Enzalutamide / ARN-509

AR antagonists; mind AR-V contexts.

Letrozole / Anastrozole

Aromatase inhibition—lower estrogen synthesis.

Mifepristone (RU486)

Glucocorticoid/progesterone receptor antagonist tool.

Ruxolitinib

JAK1/2 inhibitor—control for GH/PRL JAK–STAT readouts.

BMS-754807

IGF1R/InsR TK inhibitor (tool).

Canagliflozin / Metformin

Metabolic intervention controls (context-dependent; not classical hormone blockers).

7. Pathway schematic

Endocrine & hormone signaling overview
Endocrine and hormone pathway schematic
Legend
  1. Hypothalamic–pituitary–target gland cascades
  2. Steroid hormones → nuclear receptor transcription
  3. Peptide hormones → membrane receptors → kinases/second messengers
  4. Crosstalk with metabolism, immunity, and TME

8. Pathway biology overview

Endocrine signaling is shaped by timing (circadian/pulsatile dosing), dose, and organ specificity—the same hormone can yield opposite phenotypes across development or disease stage. Experiments should capture receptor isoforms, cofactors, coculture composition, and systemic metabolic readouts.

  • Stress–immunity: glucocorticoids and lymphocyte apoptosis / inflammatory suppression
  • Growth–cancer: IGF axis with PI3K/Akt pro-survival programs

9. Related pathways on this site

TGF-β/SmadPI3K/Akt/mTORMAPK/ERKJAK-STATMetabolismReceptor tyrosine kinaseCell cycleApoptosisNF-κBTransmembrane transport

10. External databases & modification resources

11. References

Nuclear receptor mechanisms

  • • Mangelsdorf DJ, et al. (1995). Cell. 83(6):841-50.
  • • Heldring N, et al. (2007). Physiol Rev. 87(3):905-31.

Metabolic hormones & disease

  • • Saltiel AR, Kahn CR. (2001). Nature. 414(6865):799-806.
  • • LeRoith D. (2007). Nat Rev Cancer. 7(12):915-28.