Anti-Müllerian hormone, testosterone, and insulin-like peptide 3 as biomarkers of Sertoli and Leydig cell function during deslorelin-induced testicular downregulation in the dog.
Balogh. Orsolya O; Somoskői. Bence B; Kollár. Eszter E; Kowalewski. Mariusz P MP; Gram. Aykut A; Reichler. Iris M IM; Klein. Ruth R; Kawate. Noritoshi N; Mester. László L; Walter. Beate B; Müller. Linda L
Key Findings
- Deslorelin caused a rapid drop in serum testosterone, with aspermia appearing by 2‑3 weeks and testosterone rebounding by week 15.
- Serum AMH levels rose after sperm loss and reached the assay’s maximum, indicating Sertoli‑cell changes.
- INSL3 and its receptor RXFP2 expression dropped, showing Leydig‑cell down‑regulation during treatment.
- Testicular LH‑receptor expression fell while androgen‑receptor levels stayed stable, suggesting LH insensitivity but preserved androgen sensitivity.
- AMH and INSL3 proved to be sensitive biomarkers of Sertoli and Leydig cell function during GnRH‑agonist‑induced testicular suppression.
Practical Outcomes
- If you experiment with GnRH‑agonists to modulate testosterone, tracking AMH and INSL3 in blood could tell you how deeply the testes are suppressed and when they start recovering. Expect a quick drop in testosterone, but be aware the effect is temporary and involves complex testicular cell changes, so dosing strategies should consider rebound timing and potential impacts on fertility.
Summary
The study shows that a GnRH‑agonist (deslorelin) quickly shuts down testosterone production in male dogs, then testosterone comes back after a few weeks. During this shutdown, the hormone AMH shoots up while INSL3 falls, reflecting changes in the cells that support sperm and hormone production. These hormone shifts suggest AMH and INSL3 could be useful markers to track how the testes respond to GnRH‑agonist use.
Abstract
The role of anti-Müllerian hormone (AMH) and insulin-like peptide 3 (INSL3) in male infertility is not fully understood. We used the downregulated testis as a model of gonadotropin-dependent infertility. Serum testosterone and AMH concentrations were studied in five adult male Beagles implanted (day 0) with 4.7 mg deslorelin (Suprelorin®, Virbac) (DES group). Testicular expression of LH receptor (LHR) and androgen receptor (AR), AMH, type 2 AMH receptor (AMHR2), INSL3 and its receptor (RXFP2) was evaluated 112 days (16 weeks) after deslorelin treatment by qPCR and immunohistochemistry, and compared to untreated adult (CON, n = 6) and prepubertal (PRE, n = 8) dogs. Serum testosterone concentration decreased significantly by the onset of aspermia on study day 14 (four dogs) or day 21 (one dog), and was baseline on day 105 (week 15). In contrast, serum AMH started to increase only after the onset of aspermia and reached the maximum detectable concentration of the assay by day 49-105 in individual dogs. Testicular LHR gene expression in DES was lower than in CON and PRE (P < 0.0001), while AR gene expression in DES was similar to CON and significantly higher than PRE (P < 0.0001). Testicular AMH expression in DES was intermediate compared to the lowest mRNA levels found in CON and the highest in PRE (P ≤ 0.006). AMHR2 gene expression was similar between groups. AMH protein was detected in Sertoli cells only, while AMHR2 immunoreactivity was principally detected in Leydig cells which appeared to be increased in DES. INSL3 and RXFP2 gene expression was significantly downregulated in the DES testis along with noticeably weak Leydig cell immunosignals compared to CON. In conclusion, deslorelin treatment caused testicular LH insensitivity without affecting androgen sensitivity, and de-differentiation of Sertoli and Leydig cells. In DES, upregulation of the AMH-AMHR2 feed-back loop and downregulation of the INSL3-RXFP2 feed-forward loop are paracrine-autocrine mechanisms that may additionally regulate testosterone production independent of gonadotropins. Our results support AMH and INSL3 as unique biomarkers and paracrine-autocrine regulators of testis function involved in the intimate interplay between Sertoli and Leydig cells.
Study Information
pubmed
2021
2021-08-15T00:00:00.000Z
10.1016/j.theriogenology.2021.08.017
16
77