Serum-intratesticüler testosteron oranı: fizyolojik temel, klinik önem ve insan spermatogenezi bağlamında türetme yöntemleri

Özet (abstract)

Testosterone is the primary androgen driving spermatogenesis, yet clinical practice relies on serum testosterone measurements while the functionally critical compartment is intratesticular testosterone (ITT). The testis maintains an extraordinary gradient: ITT concentrations in healthy men range from 500 to 1000 nmol/L, approximately 50 to 100 times higher than serum testosterone (10–30 nmol/L). This gradient has a clear functional basis and represents a physiological prerequisite for normal sperm production. Despite its physiological centrality, the relationship between serum and intratesticular testosterone remains poorly understood in clinical practice, and no validated non-invasive tool currently exists to assess ITT in routine settings. This narrative review synthesizes current evidence on the physiological basis, quantitative characteristics, and clinical significance of the ITT/serum testosterone ratio, and evaluates methods by which the clinician can derive ITT without invasive testicular sampling. We conducted a comprehensive literature search of PubMed and Web of Science, covering human and experimental studies published between 2000 and 2025, focusing on intratesticular androgen concentrations, cellular mechanisms of androgen action, hormonal contraception trials, and surrogate biomarker development. Testosterone acts primarily via androgen receptors on Sertoli and peritubular myoid cells — not directly on germ cells — and conditional androgen receptor knockout models confirm that Sertoli cell androgen signalling is indispensable for meiotic progression and spermiogenesis. Experimental gonadotropin suppression reducing ITT to serum-equivalent levels impairs spermatogenesis even when serum testosterone is normal, demonstrating that the high ITT gradient per se is required. Serum testosterone correlates poorly with ITT, particularly during hormonal manipulation. Among candidate non-invasive biomarkers, insulin-like factor 3 (INSL3) — constitutively secreted by Leydig cells — shows the strongest correlation with ITT under experimental conditions; 17-hydroxyprogesterone (17-OHP) reflects steroidogenic flux and provides complementary information. Combined biomarker approaches incorporating luteinizing hormone, INSL3, and 17-OHP offer a practical clinical algorithm for ITT estimation, though validated equations for routine use remain to be established. The ITT/serum testosterone ratio is a fundamental parameter for male reproductive endocrinology. Development of validated non-invasive algorithms for ITT estimation represents a key frontier, with immediate implications for testosterone replacement therapy safety, fertility preservation, and the management of hypogonadotropic hypogonadism. Graphical abstract illustrating the ITT/serum testosterone ratio and clinical biomarkers. Schematic representation of the intratesticular testosterone (ITT) compartment and its relationship to serum testosterone in the context of human spermatogenesis. The left panel depicts the testicular cross-section showing the interstitial Leydig cells (LH → testosterone biosynthesis) and the seminiferous tubules containing Sertoli cells and developing germ cells. The central gradient indicates the approximately 50–100-fold higher ITT (500–1000 nmol/L) relative to serum testosterone (10–30 nmol/L). The upper right panel shows the hormonal signalling pathway (hypothalamus → GnRH → pituitary → LH/FSH → Leydig/Sertoli cells) and the negative feedback loop disrupted by exogenous testosterone replacement therapy (TRT). The lower right panel illustrates the clinical biomarker panel for non-invasive ITT estimation: serum testosterone, LH, INSL3 (insulin-like factor 3), and 17-OHP (17-hydroxyprogesterone). The bottom panel contrasts the outcomes of normal ITT (active spermatogenesis) versus ITT suppression by TRT (azoospermia/severe oligozoospermia). Abbreviations: GnRH, gonadotropin-releasing hormone; LH, luteinising hormone; FSH, follicle-stimulating hormone; INSL3, insulin-like factor 3; 17-OHP, 17α-hydroxyprogesterone; TRT, testosterone replacement therapy.

Yazarların özeti; kaynağından alınmıştır. Reproductive Biology and Endocrinology, 2026 · DOI ↗