Fasting Enhances Pyroglutamyl Peptidase II Activity in Tanycytes of the Mediobasal Hypothalamus of Male Adult Rats.
Fasting down-regulates the hypothalamus-pituitary-thyroid (HPT) axis activity through a reduction of TRH synthesis in neurons of the parvocellular paraventricular nucleus of the hypothalamus (PVN). These TRH neurons project to the median eminence (ME), where TRH terminals are close to the cytoplasmic extensions of β2 tanycytes. Tanycytes express pyroglutamyl peptidase II (PPII), the TRH-degrading ectoenzyme that controls the amount of TRH that reaches the anterior pituitary. We tested the hypothesis that regulation of ME PPII activity is another mechanism by which fasting affects the activity of the HPT axis. Semiquantitative in situ hybridization histochemistry data indicated that PPII and deiodinase 2 mRNA levels increased in tanycytes after 48 hours of fasting. This increase was transitory, followed by an increase of PPII activity in the ME, and a partial reversion of the reduction in PVN pro-TRH mRNA levels and the number of TRH neurons detected by immunohistochemistry. In fed animals, adrenalectomy and corticosterone treatment did not change ME PPII activity 72 hours later. Methimazole-induced hypothyroidism produced a profound drop in tanycytes PPII mRNA levels, which was reverted by 3 days of treatment with T4. The activity of thyroliberinase, the serum isoform of PPII, was increased at most fasting time points studied. We conclude that delayed increases in both the ME PPII as well as the thyroliberinase activities in fasted male rats may facilitate the maintenance of the deep down-regulation of the HPT axis function, despite a partial reactivation of TRH expression in the PVN.
Departamento de Genética del Desarrollo y Fisiología Molecular (I.L., R.M.U., L.J.-H., P.J.-B., J.-L.C.), Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México; Laboratory of Neurophysiology (A.C., M.P.), Multidisciplinary Institute of Cell Biology (Argentine Research Council and Scientific Research Commission, Province of Buenos Aires), La Plata, Buenos Aires 1900, Argentina; and Dirección de Investigaciones en Neurociencias (E.S.-J.), Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, México D.F. 14370, México.
Iván
I
Lazcano
Departamento de Genética del Desarrollo y Fisiología Molecular (I.L., R.M.U., L.J.-H., P.J.-B., J.-L.C.), Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México; Laboratory of Neurophysiology (A.C., M.P.), Multidisciplinary Institute of Cell Biology (Argentine Research Council and Scientific Research Commission, Province of Buenos Aires), La Plata, Buenos Aires 1900, Argentina; and Dirección de Investigaciones en Neurociencias (E.S.-J.), Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, México D.F. 14370, México.
Agustina
A
Cabral
Departamento de Genética del Desarrollo y Fisiología Molecular (I.L., R.M.U., L.J.-H., P.J.-B., J.-L.C.), Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México; Laboratory of Neurophysiology (A.C., M.P.), Multidisciplinary Institute of Cell Biology (Argentine Research Council and Scientific Research Commission, Province of Buenos Aires), La Plata, Buenos Aires 1900, Argentina; and Dirección de Investigaciones en Neurociencias (E.S.-J.), Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, México D.F. 14370, México.
Rosa María
RM
Uribe
Departamento de Genética del Desarrollo y Fisiología Molecular (I.L., R.M.U., L.J.-H., P.J.-B., J.-L.C.), Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México; Laboratory of Neurophysiology (A.C., M.P.), Multidisciplinary Institute of Cell Biology (Argentine Research Council and Scientific Research Commission, Province of Buenos Aires), La Plata, Buenos Aires 1900, Argentina; and Dirección de Investigaciones en Neurociencias (E.S.-J.), Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, México D.F. 14370, México.
Lorraine
L
Jaimes-Hoy
Departamento de Genética del Desarrollo y Fisiología Molecular (I.L., R.M.U., L.J.-H., P.J.-B., J.-L.C.), Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México; Laboratory of Neurophysiology (A.C., M.P.), Multidisciplinary Institute of Cell Biology (Argentine Research Council and Scientific Research Commission, Province of Buenos Aires), La Plata, Buenos Aires 1900, Argentina; and Dirección de Investigaciones en Neurociencias (E.S.-J.), Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, México D.F. 14370, México.
Mario
M
Perello
Departamento de Genética del Desarrollo y Fisiología Molecular (I.L., R.M.U., L.J.-H., P.J.-B., J.-L.C.), Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México; Laboratory of Neurophysiology (A.C., M.P.), Multidisciplinary Institute of Cell Biology (Argentine Research Council and Scientific Research Commission, Province of Buenos Aires), La Plata, Buenos Aires 1900, Argentina; and Dirección de Investigaciones en Neurociencias (E.S.-J.), Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, México D.F. 14370, México.
Patricia
P
Joseph-Bravo
Departamento de Genética del Desarrollo y Fisiología Molecular (I.L., R.M.U., L.J.-H., P.J.-B., J.-L.C.), Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México; Laboratory of Neurophysiology (A.C., M.P.), Multidisciplinary Institute of Cell Biology (Argentine Research Council and Scientific Research Commission, Province of Buenos Aires), La Plata, Buenos Aires 1900, Argentina; and Dirección de Investigaciones en Neurociencias (E.S.-J.), Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, México D.F. 14370, México.
Edith
E
Sánchez-Jaramillo
Departamento de Genética del Desarrollo y Fisiología Molecular (I.L., R.M.U., L.J.-H., P.J.-B., J.-L.C.), Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México; Laboratory of Neurophysiology (A.C., M.P.), Multidisciplinary Institute of Cell Biology (Argentine Research Council and Scientific Research Commission, Province of Buenos Aires), La Plata, Buenos Aires 1900, Argentina; and Dirección de Investigaciones en Neurociencias (E.S.-J.), Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, México D.F. 14370, México.
Jean-Louis
JL
Charli
D000315:Adrenalectomy; D000626:Aminopeptidases / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology; D063928:Ependymoglial Cells / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D005215:Fasting / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007037:Hypothyroidism; D007453:Iodide Peroxidase / Q000235:genetics; D008297:Male; D008473:Median Eminence / Q000378:metabolism*; D008713:Methimazole / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013973:Thyrotropin-Releasing Hormone / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013974:Thyroxine / Q000494:pharmacology; D000097564:Iodothyronine Deiodinase Type II
D000626:Aminopeptidases; D013956:Antithyroid Agents; D003345:Corticosterone; D007453:Iodide Peroxidase; D008713:Methimazole; D011498:Protein Precursors; D011761:Pyrrolidonecarboxylic Acid; D012333:RNA, Messenger; D013973:Thyrotropin-Releasing Hormone; D013974:Thyroxine; D000097564:Iodothyronine Deiodinase Type II; C046418:pro-thyrotropin releasing hormone; C023166:pyroglutamyl-peptidase II