BIOLOGIA MOLECULAR Y GENETICADE LA HORMONA PARATIROIDEA Y LA PROTEINA RELACIONADA CON LA HORMONA PARATIROIDEA: UNA REVISION HISTORICA HASTA LA ACTUALIDAD

Resumen

Las glandulas paratiroides fueron descubiertas a finales del siglo XIX y su funcion a principios del siglo XX era
controvertido. El rol fue definido posterior a experimentos realizados por Collip (1925) donde sometia el tejido paratiroideo
a acido clorhidrico a altas temperaturas obteniendo extractos capaces de disminuir la tetania en perros posterior a una
paratiroidectomia total, dicho extracto seria denominado hormona paratiroidea 35 anos despues. Aurbach (1959) empleo
solventes organicos para liberar el componente activo sin fragmentarlo, en combinacion con tecnicas de filtracion por gel
investigadores como Brewer (1970) lograron identificar las porciones indispensables para la funcion biologica. Ademas, el
desarrollo de la biologia molecular, inmunohistoquimica y tecnologia de ADN recombinante, permitio deducir la secuencia
de polipeptidos a partir de la copia reversa del ARNm y posteriormente sintetizar el polipeptido. En 1991, fue clonado el
receptor de hormona paratiroidea. Se identifica una proteina relacionada a la hormona paratiroidea (PTHrP) cuya actividad
biologica en la homeostasis del calcio y fosfato es indistinguible de la hormona paratiroidea, capaz de regular el crecimiento
celular y la apoptosis por via intracrina. Todo ello definido a partir experimentos de ablacion genetica y promovida por la
busqueda de la causa de la hipercalcemia maligna y el estudio de la enfermedad renal cronica.

ABSTRACT: The parathyroid glands were discovered at the end of the 19th century and its role at the beginning of the 20th
was controversial. Their role was defined later due experiments conducted by Collip (1925) where extracts of parathyroid
tissue under high temperature hydrocloric acid decrease tetany in dogs with total parathyroidectomy. This substance 35
years later would be called parathyroid hormone. Aurbach (1959) used organic solvents to isolate the active unfragmented
molecule. This combined with gel filtration techniques, allowed to researches like Brewer (1970) identify essential portions for
biological activity. In addition, the development of molecular biology, inmnohistochemistry and DNA recombinant technology,
made possible identify the polypeptide sequence by reverse mRNA and synthesize parathyroid hormone polypeptide. In 1991,
parathyroid hormone receptor was cloned. Protein related to parathyroid hormone (PTHrP) was identified due to biological
activity on calcium and phosphate homeostasis indistinguishable from the parathyroid hormone. Through experiments of genetic
ablation, the PTHrP was identified as cell growth and apoptosis regulator by an intracrine pathway. All these achievements
were promoted by the research to find the cause of malignant hypercalcemia and study chronic kidney disease.