The Anti-Müllerian Hormone Precursor (proAMH) Is Not Converted to the Receptor-Competent Form (AMHN,C) in the Circulating Blood of Mice
| Autor: | Brandi-Lee A. Leathart, Michael W. Pankhurst, Ian S. McLennan, Nicola J Batchelor |
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| Rok vydání: | 2016 |
| Předmět: |
Anti-Mullerian Hormone
Male 0301 basic medicine endocrine system medicine.medical_specialty Gonad Metabolic Clearance Rate Immunoprecipitation Blotting Western Enzyme-Linked Immunosorbent Assay Biology Mice 03 medical and health sciences 0302 clinical medicine Endocrinology Internal medicine medicine Animals Humans Protein Precursors Gonads Proprotein Receptor 030219 obstetrics & reproductive medicine Sexual differentiation urogenital system Anti-Müllerian hormone Recombinant Proteins Blot HEK293 Cells 030104 developmental biology medicine.anatomical_structure Proteolysis biology.protein Female Half-Life Hormone |
| Zdroj: | Endocrinology. 157:1622-1629 |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | Anti-Müllerian hormone (AMH) is a gonadal hormone that regulates aspects of male sexual differentiation and ovarian function. AMH is synthesized as the AMH proprotein precursor (proAMH), which is converted to a receptor-binding form (AMHN,C) by proteolytic cleavage. ProAMH appears to be the predominant species in the ovary, whereas AMHN,C is the prevalent form in circulation. The aim of this study was to determine whether cleavage of proAMH occurs before it is released from the gonad or while in circulation. The individual half-lives of the proAMH and AMHN,C were also determined, as this has important implications for understanding the mechanisms of AMH signaling. Recombinant human (rh)-proAMH or rh-AMHN,C was injected iv into mice. AMH levels were analyzed in a series of repeated blood samples using an assay that detects human, but not murine, AMH. The degree of cleavage of injected proAMH was assessed by immunoprecipitation and Western blotting. The elimination half-life curves were biphasic. The fast-phase elimination was estimated at 6 and 11 minutes for rh-proAMH and rh-AMHN,C, respectively. The slow-phase half-life estimates were 2.4 and 3.8 hours for rh-proAMH and rh-AMHN,C, respectively. Immunoprecipitation of rh-proAMH 1 hour after injection determined that no detectable conversion of proAMH to AMHN,C was occurring in circulation. The data suggest that the ratio of proAMH to AMHN,C in the circulation is not altered after it is released from the gonads and that the levels of these 2 circulating forms are likely to reflect AMH activity in the gonad. |
| Databáze: | OpenAIRE |
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