Pyrrolidon Carboxypeptidase Activities in the Hypothalamus-pituitary-thyroid and Hypothalamus-pituitary-ovary Axes of Rats with Mammary Gland Cancer Induced by N-methyl Nitrosourea

M. P. Carrera; M. J. Ramírez-Expósito; M. T. Valenzuela; M. J. García; M. D. Mayas; J. M. Arias de Saavedra; R. Sánchez; M. C. Pérez; J. M. Martínez-Martos

doi:10.1055/s-2005-861158

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2005; 37(2): 74-78
DOI: 10.1055/s-2005-861158

Original Basic

Pyrrolidon Carboxypeptidase Activities in the Hypothalamus-pituitary-thyroid and Hypothalamus-pituitary-ovary Axes of Rats with Mammary Gland Cancer Induced by N-methyl Nitrosourea

M. P. Carrera¹ , M. J. Ramírez-Expósito¹ , M. T. Valenzuela² , M. J. García¹ , M. D. Mayas¹ , J. M. Arias de Saavedra³ , R. Sánchez³ , M. C. Pérez⁴ , J. M. Martínez-Martos¹

¹Departamento de Ciencias de la Salud, Área de Fisiología, Universidad de Jaén, Jaén, Spain.
²Departamento de Radiología y Medicina Física, Unidad Mixta de Investigaciones Médicas, Universidad de Granada, Hospital Universitario San Cecilio, Granada, Spain.
³Sección de Bioquímica, Servicio de Análisis Clínicos, Hospital Universitario Médico Quirúrgico, Jaén, Spain.
⁴Sección de Inmunología, Servicio de Análisis Clínicos, Hospital Universitario Médico Quirúrgico, Jaén, Spain.

Abstract

Pyrrolidon carboxypeptidase is an omega-peptidase that hydrolyses N-terminal pyroglutamyl residues from biologically active peptides such as gonadotropin-releasing and thyrotrophin-releasing hormones. We previously described a decrease in both rat and human pyrrolidon carboxypeptidase activity with breast cancer, suggesting that gonadotropin-releasing hormone may be an important local intracrine, autocrine and/or paracrine hormonal factor in the pathogenesis of breast cancer while playing a role in the tumoral process. However, the other susceptible substrate of pyrrolidon carboxypeptidase, thyrotrophin-releasing hormone, may also be modified with breast cancer, supporting an association between breast cancer and thyroid disorders. The present work analyses soluble and membrane-bound pyrrolidon carboxypeptidase activities in the hypothalamus-pituitary-thyroid and hypothalamus-pituitary-ovary axes in N-methyl nitrosourea-induced breast cancer in rats. Our aim was to determine the possible relationship between gonadotropin-releasing hormone and thyrotrophin-releasing hormone regulation through pyrrolidon carboxypeptidase activity. We propose that pyrrolidon carboxypeptidase activity dysregulation at various local and systemic levels may participate in the initiation, promotion and progression of breast cancer induced in rat by N-methyl nitrosourea through the increase in gonadotropin-releasing hormone. Since pyrrolidon carboxypeptidase activity also acts on thyrotrophin-releasing hormone, the dysregulation of this enzyme’s activity could indirectly affect hypothalamus-pituitary-thyroid axis function, and thus potentially represent a link between the diseases of thyroid and breast cancer.

Key words

Pyroglutamyl aminopeptidase · Breast cancer · GnRH · TRH · Hypothalamus-pituitary-thyroid axis · Hypothalamus-pituitary-ovary axis

Full Text

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Dr. J. M. Martínez Martos

Área de Fisiología, Facultad de Ciencias Experimentales y de la Salud, Universidad de Jaén

Campus Universitario ‘Las Lagunillas’ · 23071 Jaén · España

Phone: +34(953)212600 ·

Fax: +34(953)212141

Email: jmmartos@ujaen.es