Chronic high prolactin levels impact on gene expression at discrete hypothalamic nuclei involved in food intake

Autor: David R. Grattan, Penelope J. Knowles, Ana Maria Ornstein, Guillermina Maria Luque, Felicitas Lopez-Vicchi, Damasia Becu-Villalobos, Papillon Gustafson, Sharon R Ladyman
Rok vydání: 2019
Předmět:
0301 basic medicine
Blood Glucose
medicine.medical_specialty
Enzyme-Linked Immunosorbent Assay
NPY
Biology
Real-Time Polymerase Chain Reaction
Biochemistry
Ciencias Biológicas
03 medical and health sciences
Eating
Mice
LEPTIN
0302 clinical medicine
Biología Celular
Microbiología
Internal medicine
Dopamine receptor D2
Orexigenic
Brown adipose tissue
Genetics
medicine
STAT5 Transcription Factor
Animals
Insulin
Receptor
AGRP
Molecular Biology
Mice
Knockout
STAT
Leptin
ARCUATE NUCLEUS
digestive
oral
and skin physiology
Arcuate Nucleus of Hypothalamus
Neuropeptide Y receptor
Immunohistochemistry
Prolactin
030104 developmental biology
Endocrinology
medicine.anatomical_structure
medicine.symptom
Weight gain
CIENCIAS NATURALES Y EXACTAS
030217 neurology & neurosurgery
Biotechnology
medicine.drug
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental BiologyREFERENCES. 34(3)
ISSN: 1530-6860
Popis: To study the pathological effects of continuous hyperprolactinemia on food intake mechanisms we used female mice that lack dopamine D2 receptors in lactotropes (lacDrd2KO). These mice had lifelong hyperprolactinemia, increased food intake, and gradual development of obesity from 5 to 10 months of age. Ongoing endogenous prolactin signaling in lacDrd2KO mice was evidenced by increased basal phosphorylation of STAT5b in hypothalamic areas related to food intake, such as the arcuate (ARN), dorsomedial (DMN), and ventromedial nuclei. In the ARN of young lacDrd2KO mice there were higher Prlr mRNA levels and in obese 10‐month‐old lacDrd2KO mice increased expression of the orexigenic genes Neuropeptide Y (Npy ) and Agouti‐related peptide, compared to controls. Furthermore, Npy expression was increased in the DMN, probably contributing to increased food intake and decreased expression of Uncoupling protein‐1 in brown adipose tissue, both events favoring weight gain. Leptin resistance in obese lacD2RKO mice was evidenced by its failure to lower food intake and a dampened response of STAT3 phosphorylation, specifically in the mediobasal hypothalamus. Our results suggest that pathological chronically high prolactin levels, as found in psychiatric treatments or patients with prolactinomas, may impact on specific hypothalamic nuclei altering gene expression, leptin response, and food intake. Fil: López Vicchi, María Felicitas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Ladyman, Sharon R.. Maurice Wilkins Centre; Nueva Zelanda. University of Otago; Nueva Zelanda Fil: Ornstein, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Gustafson, Papillon. University of Otago; Nueva Zelanda Fil: Knowles, Penelope. University of Otago; Nueva Zelanda Fil: Luque, Guillermina Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Grattan, David R.. Maurice Wilkins Centre; Nueva Zelanda. University of Otago; Nueva Zelanda Fil: Becu Villalobos, Damasia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Databáze: OpenAIRE
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