{"doi":"10.1210/clinem/dgac484","title":"A Shifting Relationship Between Sex Hormone-Binding Globulin and Total Testosterone Across Puberty in Boys","abstract":"CONTEXT: Sex hormone-binding globulin (SHBG) is associated with levels of total testosterone (total-T), and both total-T and SHBG are associated with obesity. OBJECTIVE: We aimed to clarify the nature of the relationship between testosterone and SHBG and improve our understanding of their relationships with obesity. We hypothesize that the hypothalamic-pituitary-gonadal axis contributes to the homeostasis of testosterone by increasing the production of gonadal testosterone through a feedback mechanism that might operate differently at different pubertal stages. METHODS: We investigated the dynamics of the relationship between SHBG, total-T, and body mass index (BMI) throughout puberty (from age 9 to 17) using longitudinal data obtained in 507 males. The directionality of this relationship was explored using polygenic scores of SHBG and total-T, and a two-sample Mendelian Randomization (MR) in male adults. RESULTS: Consistent with our hypothesis, we found positive relationships between SHBG and total-T at age 15 and 17 but either no relationship or a negative relationship during the earlier time points. Such shifting relationships explained age-related changes in the association between total-T and BMI. Polygenic scores of SHBG and total-T in mediation analyses and the two-sample MR in male adults suggested an effect of SHBG on total-T but also a somewhat weaker effect of total-T on SHBG. Two-sample MR also showed an effect of BMI on SHBG but no effect of SHBG on BMI. CONCLUSION: These results clarify the nature of the relationship between testosterone and SHBG during puberty and adulthood and shed new light on their possible relationship with obesity.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2022,"id":261195,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":499327,"name":"Daniel E. Vosberg","orcid":"0000-0002-7356-1744","position":1,"is_corresponding":false},{"id":255764,"name":"Zdenka Pausová","orcid":"0000-0002-7784-1380","position":2,"is_corresponding":false},{"id":255768,"name":"Tomáš Paus","orcid":"0000-0003-1495-9338","position":3,"is_corresponding":false},{"id":509584,"name":"Zhijie Liao","orcid":"0000-0003-2351-0022","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T00:26:12.158801Z","pmid":"35965384","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}