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[The parathyroid gland under normal and experimental conditions].

Since Sandström reported the first detailed description of the parathyroid glands of human beings in 1880, and Lever first described the ultrastructure of the parathyroid chief cells of rat in 1957, a large number of light and electron microscopic studies have been done on the parathyroid glands of numerous animal species under normal and experimental conditions. This review deals with the comparative morphology of the parathyroid glands in amphibians, reptiles, birds and mammals under normal conditions, and the problem concerning the effects of various experimental conditions on the parathyroid glands in mice, rabbits and hamsters. The parathyroid glands were recognized in all vertebrate animals higher than fish, and arose from the third and fourth branchial pouches. Several animals, such as the newt, lizard, gecko, mouse, rat, hamster and gerbil, had only two parathyroid glands, but most animals had four. In mammals, most of the parathyroid glands were closely associated with the thyroid gland, but in amphibians, reptiles and birds, the glands separated from the thyroid gland. In some mammals, the parenchymal cells of the parathyroid gland were classified under a light microscope into two main types of cells: chief cells and oxyphil cells. Examinations under an electron microscope also showed the chief cells having many cell organelles and the oxyphil cells filled with numerous mitochondria in the parathyroid glands of human beings, monkeys, cows, horses, bats and turtles. In addition, the chief cells in most animals were classified at the light microscopic level into light cells and dark cells, moreover the chief cells were also electron microscopically divided into a light and dark type showing different functional phases of a single cell type when osmium or glutaraldehyde fixative was used. However, it is widely accepted today that differences in cytoplasmic density of the chief cells are due to artifacts produced in the process of tissue preparation. The parenchymal cells of the parathyroid gland of the newt were divided into the basal cells (supporting cells) and the suprabasal cells (chief cells). In the parathyroid gland of the frog and toad, blood vessels and connective tissues were not present. In the parathyroid gland of the rabbit and hamster, the water-clear cell was observed. In the electron microscopic radioautograph of the parathyroid gland treated with 3H-leucine, most of the silver grains were seen over cisternae of the granular endoplasmic reticulum at 15 minutes, over the Golgi complexes at 30 minutes, and over secretory granules at 60 minutes.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

Ultrastructure of the water-clear cell in the parathyroid gland of SAMP6 mice.

Although the parathyroid water-clear cell is very rare, it has clinical significance because of its association with parathyroid hyperplasia or adenoma. SAMP6, a substrain of senescence-accelerated mouse, was developed as an animal model for senile osteoporosis. We investigated the morphology of the parathyroid glands in SAMP6 and age-matched normal mouse SAMR1. The parathyroid water-clear cells, which contained numerous vacuoles and the crystalloid inclusions, were found in SAMP6 mice at 5, 8 and 12 months of age. It was noted that the number of water-clear cells increased with aging, which are fairly consistent with the change of the serum parathyroid hormone (PTH) level. We did not find any water-clear cells in the parathyroid glands of SAMR1 mice. The existence of water-clear cells may represent hyperfunction of the parathyroid glands in SAMP6.

Aging, Premature↗

The calcimimetic R-568 increases vitamin D receptor expression in rat parathyroid glands.

We previously demonstrated that extracellular calcium regulates vitamin D receptor (VDR) expression by parathyroid cells. Since the calcimimetic R-568 potentiates the effects of calcium on the calcium-sensing receptor, it was hypothesized that administration of R-568 may result in increased VDR expression in parathyroid tissue. In vitro studies of the effect of R-568 on VDR mRNA and protein were conducted in cultures of whole rat parathyroid glands and human hyperplastic parathyroid glands. In vivo studies in Wistar rats examined the effect of R-568 and calcitriol alone and in combination. Incubation of rat parathyroid glands in vitro with R-568 (0.001-1 microM) resulted in a dose-dependent decrease in parathyroid hormone (PTH) secretion and an increase in VDR expression (mean +/- SE). Incubation in 1 mM calcium + 0.001 microM R-568 elicited an increase in VDR mRNA (306 +/- 46%) similar to the maximum increase detected with 1.5 mM calcium (330 +/- 42%). In vivo, VDR mRNA was increased after administration of R-568 (168 +/- 9%, P < 0.001 vs. control) or calcitriol (198 +/- 16%, P < 0.001 vs. control). Treatment with R-568 also increased VDR protein in normal rat parathyroid glands and in human parathyroid glands with diffuse, but not nodular, hyperplasia. In conclusion, the present study shows that the calcimimetic R-568 exerts a stimulatory effect on VDR expression in the parathyroid glands of study models and provides additional evidence for the use of calcimimetics in the treatment of secondary hyperparathyroidism.

Aniline Compounds↗

Parathyroid hormone 7-84 induces hypocalcemia and inhibits the parathyroid hormone 1-84 secretory response to hypocalcemia in rats with intact parathyroid glands.

Biologic effects of large C-terminal parathyroid hormone (PTH) fragments, opposite to those of N-terminal PTH, have been demonstrated. C-terminal PTH fragments are co-secreted with N-terminal PTH from the parathyroids. The aim of our study was to examine whether C-terminal PTH 7-84 regulates secretion of PTH 1-84 and affects the expression of genes of relevance for parathyroid function, PTH, calcium-sensing receptor (CaR), PTH type 1 receptor (PTHR1), and PTH-related peptide (PTHrP) genes in rat parathyroid glands. PTH 7-84 induced a significant decrease in plasma Ca2+ in rats with intact parathyroid glands. Despite the reduction of plasma Ca2+, no stimulation of PTH 1-84 secretion took place. Furthermore, the PTH 1-84 secretory response to EGTA-induced acute and severe hypocalcemia was significantly inhibited by PTH 7-84. During recovery from hypocalcemia, plasma Ca2+ levels were significantly lower in the PTH 7-84-treated group, as compared with the vehicle group, and at the same time plasma PTH 1-84 levels were significantly suppressed. The expression of PTH, CaR, PTHR1, and PTHrP genes in the rat parathyroid glands was not affected by PTH 7-84. The peripheral metabolism of PTH 1-84 was not affected by PTH 7-84. PTH 7-84 did not cross-react with the rat bioactive PTH 1-84 assay. In normal rats with intact parathyroid glands, PTH 7-84 inhibited the PTH 1-84 secretory response to hypocalcemia and induced a significant decrease in plasma Ca2+. These effects of PTH 7-84 on PTH 1-84 secretion and on plasma Ca2+ levels were not associated with significant changes in PTH, PTHR1, CaR, and PTHrP gene expressions in the rat parathyroid glands. It is hypothesized that PTH 7-84 regulates PTH secretion via an autocrine/paracrine regulatory mechanism.

Anesthetics, Dissociative↗

The Cytoscan model E-II in intraoperative parathyroid gland identification in a rabbit model.

BACKGROUND: Intraoperative parathyroid gland identification and preservation is often a challenge even in the hands of experienced surgeons as they could be indistinguishable from fat or thyroid tissue. OBJECTIVE: The goal of this study was to demonstrate the use of the Cytoscan Model E-II, which uses orthogonal polarization spectral (OPS) imaging technology, as an intravital microscope in identifying parathyroid glands intraoperatively and differentiating the parathyroid glands from fat and thyroid tissue in a rabbit model. METHODS: The necks of 4 New England white rabbits were explored with the animals under a general anesthesia. The Cytoscan was used to obtain images of the vasculature of tissue suspected to be parathyroid, fat, and thyroid tissue. These were confirmed by histologic evaluation. RESULTS: All tissues were correctly identified by the Cytoscan and confirmed by histologic analysis. There was an obvious difference in the images obtained of fatty tissue as compared with parathyroid tissues. There was also an appreciable difference between parathyroid and thyroid tissue based on the difference in vascularity. CONCLUSIONS: OPS imaging technology can be used in identifying parathyroid glands based on the difference in vascularity from fat and the pattern and density of vessels when compared with thyroid tissue in a rabbit model. SIGNIFICANCE: The Cytoscan may play a future role in real time intraoperative identification of human parathyroid glands. Future investigation is warranted.

Adipose Tissue↗

[Study on localization of hyperfunctioning parathyroid glands by 201T1-99mTc subtraction scintigraphy].

201T1-99mTc subtraction parathyroid scintigraphy assisted by computer (CASPS) was performed in 59 patients with suspected hyperparathyroidism (HPT). There were 32 patients operated on and 40 hyperfunctioning parathyroid glands histologically proven on 33 surgical explorations. Positive rate of scintigrams in surgically explored patients was preoperatively 66% (21/32) and retrospectively 78% (25/32). In seven of surgically explored patients, ten hyperfunctioning parathyroid glands could not be recognizable retrospectively. True positive rate of preoperative and retrospective localization as to each hyperfunctioning parathyroid glands were 53% (21/40) and 75% (30/40), respectively. There was a close but not statistically significant correlation between scintigraphic localization and weight of the hyperfunctioning parathyroid glands. However, visualization of hyperfunctioning parathyroid glands was statistically significant (p less than 0.05) in X2-test in correlation between ones of less and more than 0.500 g in weight. Plain 201T1-image delineated only one of 15 hyperfunctioning parathyroid glands which were less than 0.500 g in weight and subtraction image six. This result was also statistically significant (p less than 0.05) in X2-test. Subtraction technique was proved to be essential for delineating hyperfunctioning parathyroid glands which were especially less than 0.500 g in weight. There are two adenoma which concentrated 99mTc-pertchnetate rather than 201T1 chloride. Subtraction images of these cases was not useful for positive delineation and showed an area of a decreased radioactive distribution corresponding to the presence of adenoma located at the left anterior mediastinum. However, subtraction caused false positive localization in a few cases. Quantitatively analytic method on hot regions demonstrated by subtraction, which could be helpful for avoiding false negative and false positive estimation, has been developed. Results by 201T1-99mTc subtraction parathyroid scintigraphy is not necessarily satisfactory. However, this is noninvasive and is still a challenging method for preoperative localization of hyperfunctioning parathyroid glands rather than a ultrasonography and CT scan.

Adolescent↗

Fluoride stimulation of the rat parathyroid gland: an ultrastructural study.

The parathyroid glands of rats given 150 ppm fluoride in the drinking water for 10 weeks are evaluated ultrastructurally and compared to the parathyroid glands of untreated rats. As a result of fluoride ingestion, the majority of the parathyroid cells are dark chief cells, indicating that these cells are in the active stages of the secretory cycle. More significantly, in the fluoride-treated rats, the cytoplasmic organelles of the dark chief cells are even more developed that those seen in the dark chief cells of untreated rats. The dark cells contain an electron-dense cytoplasm with abundant lamellar arrays of rough endoplasmic reticulum, spiral aggregations of free ribosomes, multiple dilated Golgi complexes, and increased numbers of secretory granules. The cells are at a minimum dimension with maximum tortuosity of the plasma membranes; and, as a result, large intercellular spaces are often seen between contiguous cells. Based on these observations, it is suggested that, in the fluoride-treated rat, a type of secondary hyperparathyroidism develops resulting in an increase in the organelles involved in protein synthesis and secretion.

Animals↗

Proliferation in hyperplastic human and normal rat parathyroid glands: role of phosphate, calcitriol, and gender.

BACKGROUND: Parathyroid gland hyperplasia develops in azotemic patients. A phosphate excess and calcitriol deficiency play critical roles in its development. Our goals were to determine whether differences in serum phosphate values at parathyroidectomy (PTX) in hemodialysis patients with refractory hyperparathyroidism: (1) correlated with parathyroid cell proliferation; and (2) affected the antiproliferative response to in vitro calcitriol. Studies were also performed to determine whether the phosphate concentration in the medium affected the antiproliferative response to calcitriol, and whether a high phosphate diet and calcitriol treatment affected parathyroid cell proliferation and parathyroid hormone (PTH) levels in normal rats. METHODS: Forty-seven parathyroid glands from 19 hemodialysis patients were obtained at PTX. Flow cytometry was used to determine cell proliferation (percent cells in S phase) in excised parathyroid glands. Similarly, cell proliferation was determined in parathyroid tissue incubated for 24 hours in medium with or without 10(-7) mol/L calcitriol and with 1 or 4 mmol/L phosphate. In normal rats, the effect of 3 days of a high phosphate diet (1.2% P) and calcitriol treatment (100 pmol/kg) on PTH values and cell proliferation was evaluated. RESULTS: In cells from freshly removed parathyroid glands obtained at PTX from hemodialysis patients, there were no significant correlations between the percent cells in S phase and age, gender, and serum phosphate, calcium, and PTH. While incubation of parathyroid tissue with 10(-7) mol/L calcitriol did reduce cell proliferation (P < 0.001), both the pre-PTX serum phosphate value (P= 0.003) and female gender (P=0.003) were associated with a decreased response to calcitriol. Incubation of parathyroid tissue in medium containing 4 mmol/L phosphate did not increase cell proliferation. In normal rats, a high phosphate diet for 3 days increased cell proliferation (P < 0.05) and PTH levels (P < 0.05), and calcitriol treatment was without effect. CONCLUSION: Our findings suggest a high phosphate burden, as well as female gender, favor parathyroid cell proliferation and both may reduce the inhibition of parathyroid function by calcitriol.

Adult↗

The oxyphil cell in abnormal parathyroid glands. A study of 114 cases.

The parathyroid oxyphil cell is apparently capable of parathyroid hormone secretion. To investigate the significance of oxyphil cells in abnormal human parathyroid glands, we compared histologic and clinical features in a retrospective study of 114 cases of hyperparathyroidism, Parathyroid glands were classified by the presence or absence of significant numbers of oxyphil cells. Significant numbers of oxyphil cells were found in 91% of all cases of secondary hyperparathyroidism, 69% of all cases of single adenoma, and 55% of all cases of primary multiple-gland hyperparathyroidism. Oxyphil cells are more common in women. Among cases of primary multiple-gland hyperparathyroidism, oxyphil cells were associated with greater mean serum calcium levels (P = .003). The oxyphil cell of the parathyroid gland is associated with hyperparathyroidism, and may secrete more hormone than the chief cell.

Adult↗

Nuclear DNA analysis of hyperplastic parathyroid glands in multiple endocrine neoplasia type I.

Twenty-four hyperplastic parathyroid glands from 11 patients with multiple endocrine neoplasia type I (MEN-I), and 36 hyperplastic parathyroid glands in 15 patients with sporadic primary hyperparathyroidism, ie, not associated with MEN, were analyzed for DNA by flow cytometry. Sixteen of 24 hyperplastic parathyroid glands from patients with MEN-I were DNA diploid, and eight were DNA aneuploid. Thirty-three of 36 hyperplastic parathyroid glands from patients without MEN were DNA diploid, and only three were DNA aneuploid. The mean percentage of 4c level (a measure of the G2M phase of the cell cycle) of DNA diploid hyperplastic parathyroid glands taken from patients with MEN-I was 8.1% +/- 4.5%, which is significantly higher than the 3.5% +/- 3.4% for those taken from patients without MEN. Our results show that there is a difference in nuclear DNA content between hyperplastic parathyroid glands in patients with MEN-I and those in patients without MEN.

Aneuploidy↗

Oxyphil cells of parathyroid glands in chronic renal failure may not secrete parathyroid hormone.

To evaluate the function of parathyroid oxyphil cell in chronic renal failure, we studied the histopathological findings of 148 parathyroid glands of 42 patients (29 males, 13 females) on maintenance hemodialysis. The individual and total weights of resected parathyroid specimens in each patient were recorded. Using the morphometrical analyzing system, we measured the oxyphil cell area and total area in each excised section taken through the maximum diameter, to estimate them in each patients. According to the fractional ratio (R:oxyphil cell area/total area), patients were divided into four groups: group I (R less than 1%), group II (1% less than or equal to 5%), group III (5% less than or equal to R less than 10%) and group IV (10% less than or equal to R). There were no differences in age, duration of hemodialysis and serum C-PTH level among the different groups. There was a positive correlation not only between total glandular weight and serum C-PTH level, but also between total glandular weight and total area, and also a positive correlation was found between serum C-PTH level and total area. No tendency was found between oxyphil cell area and serum C-PTH level. However, in 15 patients whose oxyphil cell area was more than 10 mm2, there was a negative correlation between the area and serum C-PTH level. Also, in 16 patients whose R was more than 5%, there was a negative correlation between the rate and serum C-PTH level. These results suggested that oxyphil cell in chronic renal failure might not secrete PTH.

Adult↗

Positive correlation of serum bio-intact PTH(1-84) but not intact PTH with parathyroid gland size in hemodialysis patients.

To evaluate the usefulness of newly-developed bio-intact parathyroid hormone (Bio-PTH) assay, which measures exclusively intact PTH(1-84) molecule, serum PTH level determined by Bio-PTH assay, in comparison with second-generation intact PTH (I-PTH) assay, was examined for its correlation with parathyroid gland size. Serum PTH was determined in 46 male HD patients, together with bone formation markers bone alkaline phosphatase, intact osteocalcin, N-terminal propeptide of type I collagen, and bone resorption markers deoxypyridinoline, pyridinoline, beta-crossLaps. Maximal diameter of parathyroid gland was determined with ultrasonography as the parathyroid gland size. Serum Ca and Pi correlated significantly with parathyroid gland size rationalizing our method to define parathyroid gland size. Serum Bio-PTH was correlated significantly in a positive manner with parathyroid gland size (R = 0.308, P = 0.0474), whereas serum I-PTH did not. Furthermore, parathyroid gland size did not exhibit a significant correlation with any of bone formation markers or bone resorption markers. The lack of correlation between bone markers and parathyroid gland size in HD patients may be explained by the occurrence of refractoriness of bone to PTH. In conclusion, serum Bio-PTH assay could provide a better assay than I-PTH assay to estimate parathyroid function in HD patients, due mainly to its exclusive correlation with parathyroid gland size.

Alkaline Phosphatase↗

[Anatomy of the parathyroid glands of the zebu (Bos indius)].

In this study, the anatomy of the parathyroid glands is examined in zebu cattle. Data have been collected on 61 parathyroids, belonging to 18 Gobra, Maure or Cross breeds animals. Four parathyroid glands have been identified: 2 cranial and 2 caudal. The former are located, either between the lateral retropharyngeal lymph node and the mandibular salivary gland in relation with the common carotid artery or on the latero-dorsal face of the pharynx at the emergency of the cranial laryngeal nerve. The later are located near the thyroid gland. Parathyroid glands are small (length = 1.1 cm, width = 0.6 cm), brown dark glands whose average weight is 169 mg. They can be easily collected in zebu cattle but attention must be payed to lymph and hematic nodes, thymus and fat connective tissue.

Animals↗

Autoregulation in the parathyroid glands by PTH/PTHrP receptor ligands in normal and uremic rats.

BACKGROUND: The secretion of parathyroid hormone (PTH) from the parathyroid glands might be regulated by autocrine/paracrine factors. We have previously shown that N-terminal parathyroid hormone-related protein (PTHrP) enhanced the secretory PTH response to low calcium in vivo and in vitro in rat parathyroid glands. N-terminal PTHrP fragments are equipotent to N-terminal PTH as ligands for the PTH/PTHrP receptor that is demonstrated in parathyroid tissue. This supports the possibility that the parathyroid cells respond to PTH/PTHrP receptor ligands and as such are target for an autoregulatory action of PTH and PTHrP. Our aim was to search for the PTH/PTHrP receptor in rat parathyroid glands and to examine the effects of PTHrP 1-40 on PTH secretion in in vivo models of secondary hyperparathyroidism (HPT) in uremic rats. METHODS: PTH secretion was examined during ethyleneglycol tetraacetic acid (EGTA)-induced hypocalcemia both with and without PTHrP. Five groups, each of six normal rats, received a bolus of increasing doses of 0.1, 1.0, 10, and 100 microg of PTHrP 1-40, or vehicle only. Chronic renal failure (CRF) was induced by 5/6 nephrectomy. One group of 12 CRF rats received a standard diet, while another CRF group of 18 rats received a high phosphorus diet to induce more severe HPT. After 8 weeks of uremia, the rats were infused with EGTA and PTHrP 1-40 or vehicle. The presence of the PTH/PTHrP receptor in the rat parathyroid glands was examined by reverse transcription-polymerase chain reaction (RT-PCR) technique. PTH was measured by a rat PTH assay that does not cross-react with PTHrP. RESULTS: In a dose-related manner, PTHrP enhanced the PTH response to hypocalcemia in normal rats. A similar rate of decrease of plasma Ca++ was induced by EGTA in all experimental groups. In CRF rats, plasma creatinine (0.99 +/- 0.10 mmol/L vs. 0.33 +/- 0.01 mmol/L, P < 0.001) and plasma PTH (226 +/- 32 pg/mL vs. 69 +/- 16 pg/mL, P < 0.001) levels were significantly increased. The CRF rats on high phosphorus diet had significant hypocalcemia (Ca++, 1.04 +/- 0.02 mmol/L vs. 1.28 +/- 0.03 mmol/L, P < 0.001), hyperphosphatemia (3.48 +/- 0.3 mmol/L vs. 2.25 +/- 0.1 mmol/L, P < 0.001) and severe secondary HPT, PTH (984 +/- 52 pg/mL vs. 226 +/- 32 pg/mL, P < 0.001) compared to CRF rats on a standard phosphorus diet. The maximal PTH response to hypocalcemia was enhanced in CRF rats (maximum PTH 382 +/- 58 pg/mL vs. 196 +/- 29 pg/mL in normal rats, P < 0.01) and further enhanced by PTHrP 1-40 to 826 +/- 184 pg/mL (P < 0.01). The secretory capacity of the parathyroid glands in response to low Ca++ was severely diminished in uremia. In CRF rats given a high phosphorus diet, the basal PTH levels were at the upper part of the calcium/PTH curve, and the induction of more marked hypocalcemia did not stimulate PTH secretion further (maximum PTH 1475 +/- 208 pg/mL vs. basal 1097 +/- 69 pg/mL, NS). PTHrP, however, further enhanced the maximal PTH levels significantly (maximum PTH 3142 +/- 296 pg/mL, P < 0.01). The presence of the PTH/PTHrP receptor in the rat parathyroid glands was confirmed by RT-PCR technique. CONCLUSION: PTHrP enhanced significantly, in a dose-related manner, the low Ca++-stimulated PTH secretion in normal rats. The PTH/PTHrP receptor is present in rat parathyroid glands. The impaired secretory capacity of the parathyroid glands in uremic rats is significantly enhanced by PTHrP. An autocrine/paracrine role in the parathyroid glands of the PTH/PTHrP receptor targeting peptides, PTHrP and PTH, is suggested. Thus, it is hypothesized that PTH during hypocalcemia might have a positive auto-feedback regulatory role on its own secretion.

Animals↗

Identification and purification of parathyroid hypertensive factor from organ culture of parathyroid glands from spontaneously hypertensive rats.

Parathyroid hypertensive factor (PHF) is a newly described hypertensive factor isolated from the plasma of spontaneously hypertensive rats (SHR). Recent studies have suggested that the primary origin of PHF is the parathyroid gland (PG). In the present investigation, PG from spontaneously hypertensive rats (SHR), as well as from normotensive rats, were isolated and maintained in culture. The PG from SHR, but not normotensive rats, released PHF into the culture medium. Omission of calcium from the culture medium stimulated the release of PHF. For purification of PHF, parathyroid gland culture medium (PGCM) was first dialyzed at 1000 mwco, and then ultrafiltered at 5000 molecular weight cut-off (mwco). PHF activity was retained in the fraction that was greater than 1000 daltons and less than 5000 daltons. Dialyzed and filtered SHR PGCM was fractionated by molecular exclusion HPLC. Biologically active PHF was collected in a discrete region. The biologically active molecular exclusion fraction was subsequently fractionated by reverse-phase HPLC (C-8). PHF was collected in a single discrete peak, which did not occur in culture medium prepared from normotensive PG in a similar manner. This biologically active peak occurred in the same position on molecular exclusion and reverse-phase HPLC as PHF purified from SHR plasma using similar procedures. Incubation of PGCM with trypsin inactivates the biological activity of PHF. The UV spectrum of PGCM PHF is identical to that obtained from purified plasma PHF. These results are consistent with the presence of a peptide moiety in PHF, and support the parathyroid origin of plasma PHF.

Animals↗

Effects of long-term treatment with ethanol on the ultrastructure of the golden hamster parathyroid gland.

The ultrastructure of the parathyroid gland in golden hamsters after long-term treatment with ethanol was studied. Male hamsters of experimental groups were given ethanol at the concentration of 7% for 3 and 5 months with food and water freely available. In the ethanol-treated hamsters, the Golgi complexes associated with many prosecretory granules were well developed and many secretory granules were located near the plasma membrane as compared with those of the control animals. Exocytotic events were observed in 5-month-treated animals. These findings suggest that the secretory activity of the parathyroid gland is stimulated after long-term treatment with ethanol.

Animals↗

Electron microscopic studies of the parathyroid gland of senile dogs.

The parathyroid gland of healthy senile dogs aged 8.5 to 15 years was compared with that of mature control dogs by examination with the electron microscope. Preparations fixed by perfusion with glutaraldehyde showed the cytoplasmic matrix of most parenchymal cells to be uniformly dense. None of the cells were of the extremely light type and dark cells were much less frequently noted than in preparations fixed by immersion in glutaraldehyde or osmium tetroxide. Syncytial cells and so-called coloid follicles were more frequent in senile dogs than in control dogs. It was suggested that the content of the latter structures is not colloid but necrotic substance hiving origin from the parenchymal cells and that perhaps the occasional cells containing large, membrane-bound inclusions may be degenerating cells which ultimately produce this necrotic substance. Oxyphil cells and mitochondria-rich cells of another type were found in all senile dogs, but not in the controls. These cells, especially the mitochondria-rich cells, frequently contained bizarre mitochondria that were modified in shape, size and arrangement. The most striking feature of these mitochondria was the concentric arrangement of elongated mitochondria which seemed to consist of densely layered cup-shaped mitochondria. Such mitochondria were noted in all senile dogs aged ten years and over. The significance of mitochondrial ple-morphism in the parathyroid gland of senile dogs was discussed.

Aging↗

Phosphorylation of parathyroid hormone by human and bovine parathyroid glands.

Human and bovine parathyroid gland slices were incubated in vitro for varying time periods with inorganic 32P and [35S]methionine or [3H]serine. Tissue was then extracted with aqueous medium, and parathyroid hormone (PTH) purified. Incorporated 32P was found to coelute with immunoreactive PTH in multiple chromatographic systems, and a peak of phosphorylated material could be resolved from the nonphosphorylated hormone by reversed phase high pressure liquid chromatography. The amino acid composition of both the phosphorylated and the nonphosphorylated entities conformed to that of the major glandular species of PTH, and phosphorylated hormone accounted for 10-20% of the total. A time course revealed slow incorporation of 32P into hormone, and after a 4-h preincubation with inorganic 32P, co-elution of 32P with both PTH and its precursor was observed. Phosphoserine was identified in purified PTH labeled with [3H]serine. Additionally dilute acid hydrolysis of PTH, labeled with [35S]methionine and containing 32P, generated an 35S-labeled fragment with which 32P co-chromatographed. The results are consistent with in vitro phosphorylation of PTH on serine residues within the NH2-terminal region of the hormone by both human and bovine glands and suggest that phosphorylation of the prohormone occurs as well.

Amino Acids↗