The prolactin/growth hormone receptor family

Area of Science:

• Endocrinology
• Molecular Biology
• Genetics

Background:

• Prolactin (PRL) and growth hormone (GH) are key hormones with widespread effects.
• Receptors for PRL and GH are found in classical target organs and other tissues, suggesting uncharacterized functions.
• The cloning of PRL and GH receptor cDNAs revealed they belong to a gene family with multiple forms.

Purpose of the Study:

• To investigate the characteristics and functions of prolactin (PRL) and growth hormone (GH) receptors.
• To explore the different forms of PRL and GH receptors, including their regulation and signaling pathways.
• To understand the genetic basis of disorders related to GH receptor mutations.

Main Methods:

• Identification and characterization of multiple PRL and GH receptor forms (long and short).
• Analysis of receptor and mRNA up- and down-regulation by PRL and GH.
• Development of an assay to measure functional activity of PRL receptor forms using reporter gene systems.
• Investigation of GH receptor gene mutations in Laron type dwarfism.

Main Results:

• Multiple receptor forms exist, including membrane-bound and soluble variants.
• Receptor expression is regulated by both hormones, with homologous down-regulation at high concentrations.
• Only the long form of the PRL receptor stimulates milk protein gene transcription, despite the short form being more abundant.
• GH receptor mutations are linked to Laron type dwarfism, affecting the GH binding region.

Conclusions:

• PRL and GH receptors form a gene family with diverse functional roles.
• Different receptor forms exhibit distinct activities, such as the long form's role in lactation.
• Signal transduction mechanisms for PRL and GH are complex and not fully elucidated.
• Genetic defects in GH receptors cause specific human disorders like Laron dwarfism.