Endothelin-1 regulates parathyroid hormone expression of human parathyroid cells.
OBJECTIVE
Parathyroid cells synthesize and release endothelin-1 (ET-1). ET-1 displays an in vitro inhibitory effect on basal parathyroid hormone (PTH) secretion and also counteracts PTH hypersecretion stimulated by low calcium. Such effects are further demonstrated in vivo, independent of the changes in calcitonin. We propose that ET-1 may regulate the pathogenesis of uremic hyperparathyroidism. However, this was not directly demonstrated in human parathyroid glands.


METHODS
Hyperplastic parathyroid glands are obtained from the surgical operation for uremic hyperparathyroidism. Cells are isolated by enzyme digestion and treated with ET-1, and are assessed for PTH mRNA expression. PTH in the plasma and the medium is measured by a newly developed method to detect the whole PTH (1-84).


METHODS
Uremic patients with severe secondary hyperparathyroidism and ultrasonography-proved hypertrophy of parathyroid glands received elective surgical approaches under general anesthesia. The resected glands were immediately taken to the laboratory for fresh isolation.


METHODS
Following ET-1 treatment, PTH mRNA expression is evaluated by RT-PCR method. ET-1 is detected with radioimmunoassay kit and PTH is measured by a new commercially available Duo PTH kit.


RESULTS
ET-1 exhibited a dose-dependent inhibitory effect (from 10(-12) - 10(-7) M) on PTH mRNA expression of parathyroid cells, either in the basal or in the low-calcium-stimulated states. Release of PTH into the medium is also gradually inhibited by the increase in ET-1 concentrations.


CONCLUSIONS
Our results demonstrate that ET-1 attenuates PTH mRNA expression in freshly isolated human parathyroid cells, and PTH release is also decreased. This result is consistent with our previously reported in vitro and in vivo experiments.
Chang
J M
JM
Department of Internal Medicine, Division of Nephrology, Kaohsiung Medical University Chung-Ho Memorial Hospital, Taiwan. sjhwang@kmu.edu.tw
Kuo
M C
MC
Chen
H M
HM
Lee
C H
CH
Lai
Y H
YH
Chen
H C
HC
Hwang
S J
SJ
D000328:Adult; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D019332:Endothelin-1 / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D010280:Parathyroid Glands / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D010281:Parathyroid Hormone / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D019332:Endothelin-1; D010281:Parathyroid Hormone; D012333:RNA, Messenger