Abstract
Objectives: Testosterone (T), the primary androgenic hormone in males, is stimulated through pulsatile secretion of LH and regulated through negative feedback inhibition at the hypothalamus and pituitary. The hypothalamic-pituitary-gonadal (HPG) axis also controls sperm production through the secretion of follicle-stimulating hormone (FSH). Negative feedback in the HPG axis is achieved in part through the binding of T to the androgen receptor (AR), which contains a highly variable trinucleotide repeat polymorphism (AR-CAGn). The number of repeats in the AR-CAGn inversely correlates with transcriptional activity of the AR. Thus, we predicted longer AR-CAGn to be associated with higher T, LH, and FSH levels. Methods: We examined the relationship between AR-CAGn and total plasma T, LH, and FSH, as well as “bioavailable” morning (AM-T) and evening (PM-T) testosterone in 722 young (21.5 ± 0.5 years) Filipino males. Results: There was no relationship between AR-CAGn and total T, AM-T, or LH (P >.25 for all). We did observe a marginally non-significant (P =.066) correlation between AR-CAGn and PM-T in the predicted direction, and a negative correlation between AR-CAGn and FSH (P =.005). Conclusions: Our results both support and differ from previous findings in this area, and study parameters that differ between our study and others, such as participant age, sample time, and the role of other hormones should be considered when interpreting our findings. While our data point to a modest effect of AR-CAGn on HPG regulation at best, the AR-CAGn may still affect somatic traits by regulating androgenic activity at peripheral tissues.
| Original language | English (US) |
|---|---|
| Article number | e22897 |
| Journal | American Journal of Human Biology |
| Volume | 29 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2017 |
Funding
Elizabeth Quinn, Katy Sharrock, Jeffrey Huang, Iram Azam, Divya Mallampati, Brian Dubin, and Laura Rogers helped with various phases of lab work with these samples. Karen Mohlke generously contributed DNA samples and PCA data. The authors especially thank the many researchers at the Office of Population Studies, University of San Carlos, Cebu, Philippines, for their central role in study design and data collection, and the Filipino participants, who generously provided their time for this study. This study was funded by the Wenner-Gren Foundation (Gr. 7356), the National Science Foundation (BCS-0542182), NIH (grants TW05596, DK078150, RR20649, ES10126, and DK056350), and institutional support from Northwestern University, Northwestern University Feinberg School of Medicine, University of Washington and University of Notre Dame. CWK, TWM, DTAE, LTG, and MGH designed the study and directed data collection. MR and DTAE conducted laboratory analysis. CPR, MR, and DTAE carried out laboratory or genetic analysis quality control. CPR and CWK analyzed the data. CPR and CWK wrote the manuscript. TWM, DTAE, LTG, MGH, and MR edited the manuscript for intellectual content.
Keywords
- HPG axis regulation
- androgen receptor
- follicle-stimulating hormone
- short tandem repeats
- testosterone
ASJC Scopus subject areas
- Anthropology
- Genetics
- Ecology, Evolution, Behavior and Systematics
- Anatomy