Cellular and Molecular Neurobiology

, Volume 39, Issue 2, pp 169–180 | Cite as

Brain Control of Sexually Dimorphic Liver Function and Disease: The Endocrine Connection

  • Belen Brie
  • Maria Cecilia Ramirez
  • Catalina De Winne
  • Felicitas Lopez Vicchi
  • Luis Villarruel
  • Eleonora Sorianello
  • Paolo Catalano
  • Ana María Ornstein
  • Damasia Becu-VillalobosEmail author
Review Paper


A multistep signaling cascade originates in brain centers that regulate hypothalamic growth hormone-releasing hormone (Ghrh) and somatostatin expression levels and release to control the pattern of GH secretion. This process is sexually fine-tuned, and relays important information to the liver where GH receptors can be found. The temporal pattern of pituitary GH secretion, which is sex-specific in many species (episodic in males and more stable in females), represents a major component in establishing and maintaining the sexual dimorphism of hepatic gene transcription. The liver is sexually dimorphic exhibiting major differences in the profile of more than 1000 liver genes related to steroid, lipid, and foreign compound metabolism. Approximately, 90% of these sex-specific liver genes were shown to be primarily dependent on sexually dimorphic GH secretory patterns. This proposes an interesting scenario in which the central nervous system, indirectly setting GH profiles through GHRH and somatostatin control, regulates sexual dimorphism of liver activity in accordance with the need for sex-specific steroid metabolism and performance. We describe the influence of the loss of sexual dimorphism in liver gene expression due to altered brain function. Among other many factors, abnormal brain sexual differentiation, xenoestrogen exposure and D2R ablation from neurons dysregulate the GHRH–GH axis, and ultimately modify the liver capacity for adaptive mechanisms. We, therefore, propose that an inefficient brain control of the endocrine growth axis may underlie alterations in several metabolic processes through an indirect influence of sexual dimorphism of liver genes.


GH GHRH Dopamine receptor; Hypothalamus Xenoestrogens Liver Gene dimorphism Growth hormone 



This work was supported by Grants from Agencia Nacional de Promoción Científica y Tecnológica, Argentina: PICT 330-2013; PICT 1343-2015; PICT 526-2016, Fundación Rene Barón, Fundación Williams, Consejo Nacional de Investigaciones Científicas y Técnicas; Pfizer 2015 Latin America ASPIRE Endo.

Author Contributions

DB was the main contributor (writing, searching, editing). BB, MCR, LV, PC, AMO, E S, and FLV, discussed ideas, helped in the outline of the review, and corrected the text.

Compliance with Ethical Standards

Conflict of interest

Paolo Catalano was a recipient of Pfizer 2015 Latin America ASPIRE Endo for young investigators. The rest of the authors have nothing to disclose.

Research Involving Human Participants and/or Animals

This is a review and does not involve human participants and/or animals.

Informed Consent

No informed consent is need.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Belen Brie
    • 1
  • Maria Cecilia Ramirez
    • 2
  • Catalina De Winne
    • 1
  • Felicitas Lopez Vicchi
    • 1
  • Luis Villarruel
    • 3
  • Eleonora Sorianello
    • 1
  • Paolo Catalano
    • 3
  • Ana María Ornstein
    • 1
  • Damasia Becu-Villalobos
    • 1
    Email author
  1. 1.Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y TécnicasBuenos AiresArgentina
  2. 2.Amgen MéxicoSanta FeMexico
  3. 3.Departament of Micro y Nanotechnology, Instituto de Nanociencia y NanotecnologíaComisión Nacional de Energia Atomica-Consejo Nacional de Investigaciones Científicas y TécnicasBuenos AiresArgentina

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