Androgen Regulation of Male Reproductive Physiology

Androgens, chiefly testosterone and its more potent metabolite dihydrotestosterone (DHT), orchestrate the development, maintenance and function of the male reproductive system. Synthesised by Leydig cells in response to pituitary luteinising hormone, testosterone binds to intracellular androgen receptors in target cells, triggering gene programmes essential for spermatogenesis, accessory gland maturation and secondary sexual characteristics. Within the testis, Sertoli cells interpret androgenic signals to support germ cell proliferation and differentiation, while peritubular myoid cells and epididymal epithelium remodel the tubular environment for sperm maturation. Beyond local actions, systemic androgen levels modulate libido, muscle mass and bone density, underscoring their pleiotropic influence. Dysregulation of androgen synthesis, receptor sensitivity or metabolic conversion gives rise to a spectrum of disorders from hypogonadism and infertility to benign prostatic hyperplasia and androgen-insensitive syndromes. Recent advances have refined our understanding of receptor dynamics, intratesticular androgen gradients and non-genomic signalling pathways, revealing new targets for therapeutic intervention and raising prospects for precision medicine in male reproductive health.

Research from Nature Portfolio

Recent studies have illuminated the spatiotemporal control of androgen receptor activation in Sertoli and Leydig cells, demonstrating that transient phosphorylation events at specific receptor residues fine-tune transcriptional output during spermatogonial differentiation. Complementary work has employed single-cell transcriptomics to chart the hormone-responsive landscape of the adult testis, uncovering previously unrecognised cell populations that express unique androgen-sensitive gene signatures linked to sperm motility and epididymal transit. A further investigation has detailed how systemic metabolic cues intersect with androgen signalling in the testis, revealing that fluctuations in energy status modulate intratesticular testosterone bioavailability through alterations in steroidogenic enzyme expression. Collectively, these contributions deepen mechanistic insight into how androgens integrate endocrine, paracrine and metabolic inputs to govern male reproductive physiology.

Androgen Regulation of Male Reproductive Physiology publication trend

The graph below shows the total number of articles in androgen regulation of male reproductive physiology across all publications each year (not limited to Nature Index journals).

Technical terms

Androgen receptor (AR): A nuclear transcription factor that binds testosterone or DHT to regulate gene expression.

5α-reductase: The enzyme that converts testosterone to the more potent androgen DHT.

Dihydrotestosterone (DHT): A biologically active androgen derived from testosterone, essential for prostate and external genital development.

Spermatogenesis: The multi-stage process by which spermatogonial stem cells develop into mature spermatozoa.

Leydig cells: Testicular interstitial cells that synthesise and secrete testosterone under luteinising hormone control.

Sertoli cells: Somatic cells in the seminiferous tubules that support and nourish developing germ cells.

References

1. Effects of proteases and protease inhibitors on the 4.5 S and 8 S androgen receptor.. Journal of Biological Chemistry (1979).
2. The effect of finasteride on spermatogenesis of Mesocricetus auratus. Acta Cirúrgica Brasileira (2008).
3. Paternal Finasteride Treatment Can Influence the Testicular Transcriptome Profile of Male Offspring—Preliminary Study. Current Issues in Molecular Biology (2021).