title: Mediobasal hypothalamic and adenohypophyseal TRH-degrading enzyme (PPII) is down-regulated by zinc deficiency.
abstract: Thyrotropin-releasing hormone (TRH) synthesized in hypothalamic paraventricular nucleus directs hypothalamus-pituitary-thyroid (HPT) axis function, regulating thyrotropin release from adenohypophysis and thyroid hormones serum concentration. Pyroglutamyl aminopeptidase II (PPII), a Zn-dependent metallopeptidase located in adenohypophysis and medial-basal-hypothalamus degrades TRH released from the median eminence and participates in HPT axis function by regulating TRH-induced thyrotropin release from adenohypophysis. It is unknown whether dietary Zn deficiency down-regulates PPII. Our aim was to compare adenohypohyseal and medial-basal-hypothalamic PPII activity and expression of adult rats fed a Zn-deficient diet (2ppm) throughout their lifespan (DD), prenatally (DC) or after weaning (CD) vs. that of animals fed a control diet (20ppm:CC). Female rats consumed a Zn-deficient or control diet from two weeks before gestation and up to the end of lactation. We analyzed adenohypophyseal and medial-basal-hypothalamic PPII activity of dams and male offspring when adults; its relation to median eminence TRH, serum thyrotropin, leptin and thyroid hormones concentration. Offspring ate the same diet as their dams (CC, DD) or were switched from dietary regime after weaning (CD, DC) and until 2.5 months of age. DD males showed decreased adenohypophyseal and medial-basal-hypothalamic PPII activity, along with high thyrotropin serum concentration. Post-weaning Zn-deficiency (CD) decreased PPII activity only in adenohypophysis and increased thyrotropin circulating levels. Zn-replenishment (DC) normalized PPII activity in both regions and serum thyrotropin concentration. Adenohypophyseal PPII activity decreased and prolactin levels increased in Zn-deficient dams. We concluded that long-term changes in dietary Zn down-regulate PPII activity independently of T3, increasing thyrotropin serum concentration, overall resembling sub-clinical hypothyroidism.
authors: Department of Neurosciences Research, National Institute of Psychiatry Ramón de la Fuente Muñiz, Mexico; ISSSTE School of Dietetics and Nutrition, Mexico.
authors: Elena
authors: E
authors: Alvarez-Salas
authors: Department of Neurosciences Research, National Institute of Psychiatry Ramón de la Fuente Muñiz, Mexico; ISSSTE School of Dietetics and Nutrition, Mexico.
authors: Viridiana
authors: V
authors: Alcántara-Alonso
authors: Department of Neurosciences Research, National Institute of Psychiatry Ramón de la Fuente Muñiz, Mexico.
authors: Gilberto
authors: G
authors: Matamoros-Trejo
authors: Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mor 62271, Mexico.
authors: Miguel Angel
authors: MA
authors: Vargas
authors: Department of Neurosciences Research, National Institute of Psychiatry Ramón de la Fuente Muñiz, Mexico.
authors: Marcela
authors: M
authors: Morales-Mulia
authors: Department of Neurosciences Research, National Institute of Psychiatry Ramón de la Fuente Muñiz, Mexico. Electronic address: gortari@imp.edu.mx.
authors: Patricia
authors: P
authors: de Gortari
mesh_terms: D000367:Age Factors; D000626:Aminopeptidases / Q000172:deficiency / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007033:Hypothalamus, Middle / Q000378:metabolism*; D007774:Lactation / Q000187:drug effects; D008297:Male; D011247:Pregnancy; D011388:Prolactin / Q000378:metabolism; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D013972:Thyrotropin / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D015032:Zinc / Q000008:administration & dosage / Q000097:blood / Q000172:deficiency*
chemical_list: D012333:RNA, Messenger; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D013972:Thyrotropin; D000626:Aminopeptidases; C023166:pyroglutamyl-peptidase II; D015032:Zinc; D011761:Pyrrolidonecarboxylic Acid
keywords: Adenohypophysis; PPII enzyme; Subclinical hypothyroidism; TSH; Thyroid axis; Zn deficiency