Comparison of the abilities of human parathyroid hormone (hPTH)-(1-34) and [Leu27]-cyclo(Glu22-Lys26)-hPTH-(1-31)NH2 to stimulate femoral trabecular bone growth in ovariectomized rats.
hPTH-(1-31)NH2, so far the smallest of the potently anabolic N-terminal fragments of the human parathyroid hormone, stimulates trabecular growth in the distal femurs of ovariectomized (OVX) rats as strongly as hPTH-(1-34) when injected at a high daily dose such as 1 nmol/100 g of body weight, but it is only about 70% as effective as hPTH-(1-34) when injected at the suboptimal 0.6 nmol/100 g of body weight. A lactam derivative of hPTH-(1-31)-NH2, [Leu27]-cyclo(Glu22-Lys26)-hPTH-(1-31)NH2, is a much more effective stimulator of adenylyl cyclase in ROS 17/2 rat osteoblast-like cells and a significantly more effective stimulator of femoral trabecular growth in OVX rats than hPTH-(1-31)NH2. We have now shown that [Leu27]-cyclo(Glu22-Lys26)-hPTH-(1-31)NH2 prevents the OVX-induced loss of femoral trabeculae significantly more effectively than hPTH-(1-34) and stimulates the thickening of the trabeculae remaining in severely depleted femoral trabecular bone of OVX rats as effectively as hPTH-(1-34) when injected at 0.6 nmol/100 g of body weight.
Whitfield
J F
JF
Institute for Biological Sciences, National Research Council of Canada, Bldg. M-54, Montreal Road Campus, Ottawa, Ontario, Canada K1A 0R6.
Morley
P
P
Willick
G
G
MacLean
S
S
Ross
V
V
Isaacs
R J
RJ
Barbier
J R
JR
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D015519:Bone Density / Q000187:drug effects / Q000502:physiology*; D001846:Bone Development / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D005260:Female; D006801:Humans; D010006:Osteoblasts / Q000201:enzymology; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D019379:Teriparatide / Q000494:pharmacology*
D010281:Parathyroid Hormone; D010446:Peptide Fragments; C116052:parathyroid hormone (1-31)-NH2, leucyl(27)-cyclo(glutamyl(22)-lysyl(26))-; D019379:Teriparatide; D000262:Adenylyl Cyclases