RESUMO
OBJECTIVE: Hepcidin reduces iron absorption by binding to the intestinal iron transporter ferroportin, thereby causing its degradation. Although short-term administration of testosterone or growth hormone (GH) has been reported to decrease circulating hepcidin levels, little is known about how hepcidin is influenced in human endocrine conditions associated with anemia. RESEARCH DESIGN AND METHODS: We used a sensitive and specific dual-monoclonal antibody sandwich immunoassay to measure hepcidin-25 in patients (a) during initiation of in vitro fertilization when endogenous estrogens were elevated vs. suppressed, (b) with GH deficiency before and after 12 months substitution treatment, (c) with hyperthyroidism before and after normalization, and (d) with hyperprolactinemia before and after six months of treatment with a dopamine agonist. RESULTS: In response to a marked stimulation of endogenous estrogen production, median hepcidin levels decreased from 4.85 to 1.43 ng/mL (p < 0.01). Hyperthyroidism, hyperprolactinemia, or GH substitution to GH-deficient patients did not influence serum hepcidin-25 levels. CONCLUSIONS: In humans, gonadotropin-stimulated endogenous estrogen markedly decreases circulating hepcidin-25 levels. No clear and stable correlation between iron biomarkers and hepcidin-25 was seen before or after treatment of hyperthyroidism, hyperprolactinemia or growth hormone deficiency.
Assuntos
Anemia/sangue , Estrogênios/fisiologia , Hepcidinas/sangue , Adolescente , Adulto , Idoso , Anemia/metabolismo , Proteína C-Reativa/biossíntese , Proteína C-Reativa/metabolismo , Agonistas de Dopamina/química , Feminino , Ferritinas/biossíntese , Ferritinas/metabolismo , Fertilização in vitro , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/metabolismo , Humanos , Hiperprolactinemia/complicações , Hipertireoidismo/complicações , Imunoensaio , Ferro/metabolismo , Masculino , Pessoa de Meia-Idade , Prolactinoma/sangue , Transferrina/biossíntese , Transferrina/metabolismo , Adulto JovemRESUMO
UNLABELLED: Secretion of cholesterol into bile is important for the elimination of cholesterol from the body. Thyroid hormone (TH) increases biliary cholesterol secretion and hepatic gene expression of adenosine triphosphate (ATP)-binding cassette, subfamily G (WHITE), member 5 (ABCG5) and ATP-binding cassette, subfamily G (WHITE), member 8 (ABCG8), two half-transporters that act as a heterodimeric complex promoting sterol secretion. In addition, nuclear liver x receptor-alpha (LXRa), also regulated by TH, induces gene expression of ABCG5/G8. We here investigated if the TH-induced stimulation of biliary cholesterol secretion is mediated by the ABCG5/G8 complex in vivo, and if so, whether LXRa is involved. Mice homozygous for disruption of Abcg5 (Abcg5(-/-) ) or Lxra (Lxra(-/-) ) and their wild-type counterparts were treated with triiodothyronine (T3) for 14 days and compared to untreated mice of corresponding genetic backgrounds. Bile was collected by gallbladder cannulation, and liver samples were analyzed for gene expression levels. Basal biliary cholesterol secretion in Abcg5(-/-) mice was 72% lower than in Abcg5(+/+) mice. T3 treatment increased cholesterol secretion 3.1-fold in Abcg5(+/+) mice, whereas this response was severely blunted in Abcg5(-/-) mice. In contrast, biliary cholesterol secretion in T3-treated Lxra(+/+) and Lxra(-/-) mice was increased 3.5- and 2.6-fold, respectively, and did not differ significantly. CONCLUSIONS: TH-induced secretion of cholesterol into bile is largely dependent on an intact ABCG5/G8 transporter complex, whereas LXRa is not critical for this effect.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Bile/metabolismo , Colesterol/metabolismo , Expressão Gênica/efeitos dos fármacos , Lipoproteínas/genética , Fígado/metabolismo , Receptores Nucleares Órfãos/genética , RNA/metabolismo , Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Membro 8 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/efeitos dos fármacos , Análise de Variância , Animais , Ácidos e Sais Biliares/metabolismo , Colesterol 7-alfa-Hidroxilase/genética , Homozigoto , Hidroximetilglutaril-CoA Redutases/genética , Lipoproteínas/efeitos dos fármacos , Receptores X do Fígado , Masculino , Camundongos , Receptores Nucleares Órfãos/efeitos dos fármacos , Fosfolipídeos/análise , Receptores de LDL/genética , Tri-Iodotironina/farmacologiaRESUMO
BACKGROUND & AIMS: Hypopituitarism is associated with dyslipidemia, and feeding hypophysectomized rats cholesterol induces severe hypercholesterolemia. This study aimed to unravel further how hypophysectomy alters cholesterol and bile acid metabolism. METHODS: Intact and hypophysectomized rats were studied during challenge with dietary cholesterol and ezetimibe and upon hormonal substitution with growth hormone, cortisone, and thyroid hormone. RESULTS: Five findings were established in hypophysectomized rats: (1) The intestinal absorption of cholesterol is doubled. (2) Treatment with ezetimibe abolishes the increases in serum and liver cholesterol. (3) Only thyroid hormone treatment normalizes the increased absorption of cholesterol. (4) The intestinal gene expression of cholesterol transporters NPC1L1 and ABCG5/G8 is unaltered, whereas the hepatic expression of ABCG5/G8 is diminished but strongly stimulated by thyroid hormone. The latter mechanism was supported by measurements of biliary cholesterol and of fecal neutral steroids. (5) The reduced hepatic expression of ABCG5/G8 and Cyp7a1 was normalized by cholesterol feeding, suggesting that other nonestablished mechanisms under pituitary control are important to maintain rats resistant to dietary cholesterol. CONCLUSIONS: The intestinal absorption of dietary cholesterol is under pituitary control largely exerted by thyroid hormone. Hepatic secretion of cholesterol and ABCG5/G8 expression are strongly stimulated in hypophysectomized rats during treatment with thyroid hormone.