# Neuroendocrine plasticity and crosstalk in pubertal development

**Authors:** Carol Fuzeti Elias, Xingfa Han, David Garcia‐Galiano, Cristina Sáenz de Miera

PMC · DOI: 10.1111/jne.70145 · Journal of Neuroendocrinology · 2026-02-19

## TL;DR

This paper explores how the brain's hypothalamus changes during puberty to control reproductive development.

## Contribution

The study reveals new insights into the neural and molecular mechanisms of sexual maturation through RNA sequencing and genetic models.

## Key findings

- The pubertal transition involves changes in the chemical phenotype of hypothalamic neurons.
- Key neurons expressing GHRH, kisspeptin, or DAT undergo site-specific innervation changes.
- Hypothalamic remodeling is crucial for triggering reproductive maturation.

## Abstract

Puberty is a critical developmental stage during which individuals acquire the capacity for sexual reproduction. This transition involves a series of complex biological events primarily orchestrated by the activation of the hypothalamo–pituitary–gonadal (HPG) axis. Central to this process are gonadotropin‐releasing hormone (GnRH) neurons, which play a key role in regulating reproductive maturation and function throughout life. However, the precise mechanisms that trigger the pubertal increase in GnRH activity remain incompletely understood. Evidence from our laboratory indicates that a profound remodeling of the hypothalamus is crucial for sexual maturation. In this review, we discuss findings from our research utilizing a combination of RNA sequencing, conditional genetic manipulation with mouse models and viral vectors, and systems neuroscience approaches. Our results reveal that the pubertal transition involves changes in the chemical phenotype and site‐specific innervation of key hypothalamic neurons. Among these neuronal populations, those expressing growth hormone‐releasing hormone (GHRH), kisspeptin, or dopamine transporter (DAT) are the focus of this review. Building upon data from other laboratories, our findings offer new insights into the neural and molecular mechanisms by which the hypothalamus orchestrates sexual maturation.

## Linked entities

- **Genes:** GNRH1 (gonadotropin releasing hormone 1) [NCBI Gene 2796], GHRH (growth hormone releasing hormone) [NCBI Gene 2691], SLC6A3 (solute carrier family 6 member 3) [NCBI Gene 6531]
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Cdkn1c (cyclin dependent kinase inhibitor 1C) [NCBI Gene 12577] {aka CDKI, Kip2, p57(kip2), p57Kip2}, Fshb (follicle stimulating hormone beta) [NCBI Gene 14308] {aka FSH, FSH-B, FSH-beta, Fshbeta}, Lep (leptin) [NCBI Gene 16846] {aka ob, obese}, Gcg (glucagon) [NCBI Gene 14526] {aka GLP-1, Glu, PPG}, Slc6a3 (solute carrier family 6 (neurotransmitter transporter, dopamine), member 3) [NCBI Gene 13162] {aka DAT, Dat1}, Kiss1 (KiSS-1 metastasis-suppressor) [NCBI Gene 280287] {aka kisspeptin, metastatin}, Mc4r (melanocortin 4 receptor) [NCBI Gene 17202] {aka Mc4-r, Pkcp}, Lepr (leptin receptor) [NCBI Gene 16847] {aka B219, LEP-R, LEPROT, Leprb, Modb1, OB-RGRP}, Ldlrap1 (low density lipoprotein receptor adaptor protein 1) [NCBI Gene 100017] {aka ARH2, Arh, Arh1, FHCB1, FHCB2}, Gpr88 (G-protein coupled receptor 88) [NCBI Gene 64378] {aka Strg}, KISS1 (KiSS-1 metastasis suppressor) [NCBI Gene 3814] {aka HH13, KiSS-1}, Igf1 (insulin-like growth factor 1) [NCBI Gene 16000] {aka C730016P09Rik, Igf-1, Igf-I}, Esr1 (estrogen receptor 1 (alpha)) [NCBI Gene 13982] {aka ER, ER-alpha, ERa, ERalpha, ESR, Estr}, GHRH (growth hormone releasing hormone) [NCBI Gene 2691] {aka GHRF, GRF, INN}, Agrp (agouti related neuropeptide) [NCBI Gene 11604] {aka Agrt, Art}, Mkrn3 (makorin, ring finger protein, 3) [NCBI Gene 22652] {aka D7H15S9-1, Zfp127}, Skull14 (skull morphology 14) [NCBI Gene 114722] {aka L10, QTL-S10.1}, Pomc (pro-opiomelanocortin-alpha) [NCBI Gene 18976] {aka ACTH, BE, Beta-LPH, Clip, Gamma-LPH, Npp}, Drd3 (dopamine receptor D3) [NCBI Gene 13490] {aka D3R}, Gh (growth hormone) [NCBI Gene 14599] {aka Gh1, Ghb1}, Ghrh (growth hormone releasing hormone) [NCBI Gene 14601] {aka GRF, Ghrf}, Ddc (dopa decarboxylase) [NCBI Gene 13195] {aka Aadc}, Mc3r (melanocortin 3 receptor) [NCBI Gene 17201] {aka MC3-R}, Nr4a2 (nuclear receptor subfamily 4, group A, member 2) [NCBI Gene 18227] {aka HZF-3, NOT, Nurr1, RNR-1, TINOR, TINUR}, LEP (leptin) [NCBI Gene 3952] {aka LEPD, OB, OBS}, Th (tyrosine hydroxylase) [NCBI Gene 21823], ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, Npy (neuropeptide Y) [NCBI Gene 109648] {aka 0710005A05Rik}, Gnrh1 (gonadotropin releasing hormone 1) [NCBI Gene 14714] {aka Gnrh, Gnrh2, LHRH, Lhrh1, Lnrh, hpg}, Prl (prolactin) [NCBI Gene 19109] {aka Gha1, Prl1a1}, LDLRAP1 (low density lipoprotein receptor adaptor protein 1) [NCBI Gene 26119] {aka ARH, ARH1, ARH2, FHCB1, FHCB2, FHCL4}
- **Diseases:** metabolic disturbances (MESH:D024821), DOPAMINE TRANSPORTER (MESH:C567730), delayed puberty (MESH:D011628), UNEXPECTED CONTENDER (MESH:D000080485), aggression (MESH:D010554), infertility (MESH:D007246), COMBINED (MESH:D053632), overnutrition (MESH:D044343)
- **Chemicals:** steroid (MESH:D013256), Saline (MESH:D012965), estradiol (MESH:D004958), dopamine (MESH:D004298), catecholamines (MESH:D002395), amino acids (MESH:D000596), glucose (MESH:D005947), fatty acids (MESH:D005227)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** J — Homo sapiens (Human), Bladder carcinoma, Cancer cell line (CVCL_M891)

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12921428/full.md

## References

75 references — full list in the complete paper: https://tomesphere.com/paper/PMC12921428/full.md

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Source: https://tomesphere.com/paper/PMC12921428