CHARACTERIZATION OF THE MOLECULAR AND FUNCTIONAL HETEROGENEITY OF GROWTH HORMONE (GH)

Most pituitary hormones are structurally heterogeneous and also show wide functional diversity. The interest of this group is focused on characterizing growth hormone heterogeneity and establishing a correlation between the structural variants of GH and its multiple functions. We have shown that GH is actually a family of proteins whose members differ from each other in their basic structure due to a number of chemical modifications (such as glycosylation, phosphorylation, proteolytic cleavage, or oligomerization) or because they are generated by alternative splicing.

Some of the molecular variants of GH seem to influence diverse aspects of metabolism pathways by means of specific biological activities that are not shared by all members of this hormone family. The pattern of molecular heterogeneity observed in the pituitary is maintained in plasma, which strongly suggests that the variants are effectively released into the circulation. We have also shown that the synthesis and/or secretion of pituitary GH variants are subject to differential regulation, since their relative concentrations change during growth and development and under different physiological and experimental conditions.

In addition, we are studying the presence and distribution of GH in extrapituitary tissues, such as the reproductive apparatus, the immune system, the eye and the brain. We have analyzed the expression of GH mRNA, quantified the amount of GH protein and studied its pattern of molecular heterogeneity in these tissues and compared it with that found in the pituitary.  We have also described some of the cells of the extrapituitary tissues where GH is found. Based on these findings we suggest that GH plays a paracrine and/or autocrine role in such tissues.
The experimental approaches employed in these studies are supported by methodologies that involve protein biochemistry, molecular biology, tissue and cell culture, quantitative and qualitative immunotechniques, as well as in vitro and in vivo bioassays.