US-2109-93R

Publications

Achievements

An In Vitro and In Vivo Investigation of the Diverse Biological Activities of Bovine Placental Lactogen	Budget	Duration
	$275,000	3 years

	Spiers, D.E.	U Missouri
	Gertler, A.	Hebrew U
	Johnson, H.D.	U Missouri
	Spain, J.	U Missouri

Final Report Abstract
In order to understand the structure-function relationship of bovine placental lactogen (bPL) and initiate production of material for in vivo testing, 28 different bPL analogues were prepared by either truncation or site-directed mutagenesis. The effect of these mutations was determined by measuring binding capacity, ability to homodimerize extracellular domains (ECDs) of several lactogenic and somatogenic receptors, and by in vitro bioassays. Two analogues were prepared in large amounts for in vivo studies. These studies (a) identified the residues responsible for the somatogenic activity of bPL (K73, G133, T188) and for both lactogenic and somatogenic activity (N-terminus, K185, Y190); (b) allowed preparation of bPL analogues with selectively abolished or reduced somatogenic activity; and (c) provided a tool to understand the kinetic difference between lactogenic and somatogenic receptors. In vivo studies using rodent and dairy models showed that bovine growth hormone (bGH) is superior to bPL in stimulating growth and lactation. Likewise, bGH has greater somatogenic activity in different age groups and thermal environments. Initial studies of bPL analog T188 suggest that its lactogenic potential is superior to bGH. Effective experimental models have now been developed and tested for analysis of new bPL analogs.