T-lymphoblast cell lines from Laron dwarfs augment basal colony formation in response to extremely high concentrations of growth hormone.
The clinical entity of Laron dwarfism is characterized by resistance to both endogenous and exogenous GH and may be due to a deficiency or absence of functional GH receptors. We previously showed that two types of hematopoietic cells derived from these patients are resistant to the in vitro growth-promoting action of GH at concentrations below 500 micrograms/L. In the current study we found that Laron T-cell lines had a mean peak augmentation of basal colony formation of 22 +/- 3.4% above baseline in response to a GH concentration of 10,000 micrograms/L. Since cloned cDNAs for human and rabbit GH receptors and rat PRL receptors show a high degree of sequence homology, we undertook studies of PRL action in cells from patients with Laron dwarfism to determine if the Laron defect was also associated with PRL unresponsiveness. Quantitating the augmentation of colony formation by T-lymphoblast cell lines established from three Laron dwarfs, we found normal responsiveness to PRL at concentrations of 25-10,000 micrograms/L. It is, thus, possible that the responsiveness of Laron T-cell lines to very high concentrations of GH could be mediated through an intact PRL (or other lactogenic) receptor based on the known affinity of GH for these receptors in other systems. These data suggest that cells from patients with Laron dwarfism have normal in vitro responsiveness to PRL and that the defect in Laron dwarfism appears to be specific to the GH receptor-effector pathway. It remains to be determined whether intact alternative lactogenic receptor mechanisms subserve any clinical effects of GH in patients with Laron dwarfism.
Geffner
M E
ME
Department of Pediatrics, UCLA Medical Center 90024.
Bersch
N
N
Lippe
B M
BM
Golde
D W
DW
D002460:Cell Line / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004393:Dwarfism, Pituitary / Q000378:metabolism*; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D011388:Prolactin / Q000494:pharmacology; D011986:Receptors, Somatotropin / Q000172:deficiency / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects*
D011986:Receptors, Somatotropin; D011388:Prolactin; D013006:Growth Hormone