Proliferation of parathyroid cells negatively correlates with expression of parathyroid hormone-related protein in secondary parathyroid hyperplasia.
BACKGROUND
Parathyroid hormone-related protein (PTHrP) is now suspected to act as an autocrine or paracrine regulator of cell growth or differentiation, although it was originally reported as a hypercalcemic substance in malignancies. This study was performed to assess the relationship between PTHrP expression and cell proliferation in human parathyroid glands.


METHODS
The localization of PTH and PTHrP was studied in 42 samples of hyperplastic parathyroid from 14 long-term hemodialysis cases with immunohistochemistry and in situ hybridization. Results were compared with proliferative activity (proliferating cell nuclear antigen index: counts of proliferating cell nuclear antigen-positive cells/100 cells). The localization of the PTH/PTHrP receptor was also examined. Ten normal glands were studied as controls.


RESULTS
In hyperplasia, cells positive for PTH, PTHrP, or both were observed immunohistochemically. The areas expressing PTHrP mRNA completely coincided with those positive for PTHrP immunohistochemically. Oxyphilic or transitional oxyphilic cells were consistently positive for PTHrP. PTH/PTHrP receptors were located in the cytoplasmic membrane in most parathyroid cells. Proliferating cell nuclear antigen-positive cells were rare in normal glands with an index of 0. 22 +/- 0.09 (mean +/- sem). They were significantly increased in hyperplastic cases but less for PTHrP-positive than for -negative cells (1.25 +/- 0.16 as compared with 7.80 +/- 0.52; P < 0.0001).


CONCLUSIONS
The observed low level of proliferation of PTHrP-positive cells suggests a functional role for PTHrP as a possible growth suppressor in the human parathyroid.
Matsushita
H
H
Departments of Pathology, Endocrinology, Nephrology, Endocrine Surgery, and the Epidemiological Research Center, Toranomon Hospital, Minatoko, Japan. hiroshi.matsushita@toranomon.gr.jp
Hara
M
M
Endo
Y
Y
Shishiba
Y
Y
Hara
S
S
Ubara
Y
Y
Nakazawa
H
H
Suzuki
N
N
Kawaminami
K
K
Kido
T
T
Li
Q
Q
Grimelius
L
L
D000328:Adult; D001483:Base Sequence; D002455:Cell Division; D005260:Female; D015870:Gene Expression; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006965:Hyperplasia; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D015345:Oligonucleotide Probes / Q000235:genetics; D010280:Parathyroid Glands / Q000378:metabolism* / Q000473:pathology*; D010281:Parathyroid Hormone / Q000378:metabolism; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone / Q000378:metabolism
D015345:Oligonucleotide Probes; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D012333:RNA, Messenger; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone