Biomedical subjects

E Hubina

Publications and source records attributed to E Hubina.

7 recordsLinked to original sources

PubMed2005

Novel molecular aspects of pituitary adenomas.

Ghrelin stimulates while somatostatin inhibits GH release and they thus serve as functional antagonists. We have compared their effects on cell proliferation. Ghrelin stimulates while somatostatin inhibits cell proliferation in most tissues and cell lines. Here we show that ghrelin and desoctanoyl ghrelin stimulate cell proliferation in rat pituitary cell line (GH3), and these effects could be inhibited with mitogen-activated protein kinase (MAPK), tyrosine kinase and protein kinase C inhibitors. Somatostatin and its analogs negatively regulate the growth of pituitary cells, and we now show that they inhibit MAPK activation. We hypothesised that one of the mechanisms involved in the somatostatin effect is a stimulation of cell cycle inhibitor p27, as pituitary adenomas have decreased p27 peptide content. Both octreotide and a new somatostatin analog SOM230 treatment resulted in an upregulation of p27 protein levels in human somatotrophinoma cells. In summary, we suggest that ghrelin and somatostatin have opposite effects on somatotroph cells not just at the level of GH release but also in terms of cell proliferation. Ghrelin may play a role in pituitary tumorigenesis via an autocrine/paracrine pathway. Our results also suggest that the antiproliferative effect of somatostatin analogs octreotide and SOM230 involve the up-regulation of p27 and down-regulation of the MAPK pathway in human somatotrophinomas.

Adenoma↗

PubMed2004

The effect of gender and age on growth hormone replacement in growth hormone-deficient patients.

We analyzed the effect of growth hormone replacement therapy (36 months) analyzed at a dose adjusted to maintain serum insulin-like growth factor-I level between the median and the upper end of the age-related reference range on bone mineral density, body composition, and carbohydrate metabolism with respect to gender and age in 20 adult patients (9 women, 11 men, mean age: 43 years, range: 21-61 years). The lumbar and femoral T-score was increased after 12 and after 18 months of therapy respectively in men (p < 0.001 and p = 0.002), but did not changed significantly in women. The increase of femoral T-score was greater in young men (< or = 45 years, n = 6) than old men (> 45 years, n = 5, p < 0.001). Body fat was lower in men than in women after 6 months (p = 0.002). The waist/hip ratio only decreased in women (p = 0.044). The waist circumference decreased in both genders after 6 months of therapy (p < 0.001), but more markedly in females than in males (p < 0.05). The sum of skinfold thicknesses was reduced in males after 6 months of therapy (p < 0.001). Changes in body composition parameters measured were independent of age. The glycosylated hemoglobin increased without sex or age difference after 12 months of initiation of therapy (p < 0.001), but fasting glucose and insulin levels did not change during the therapy. Our results indicate that the effect of growth hormone replacement on bone mineral content in adults is age- and gender-dependent, gender dependent on body composition, but independent of age and gender on carbohydrate metabolism.

Adult↗

PubMed2003

Effects of 24 months of growth hormone (GH) treatment on serum carboxylated and undercarboxylated osteocalcin levels in GH-deficient adults.

We studied the effect of growth hormone (GH) replacement on bone mineral density (BMD) and some parameters of bone metabolism, including undercarboxylated osteocalcin (ucOC), an independent predictive marker of fracture risk, which has not been previously determined or compared during GH treatment. Measurements were performed at baseline and after 6, 12, 18 and 24 months of the initiation of the GH therapy in 21 adult patients with GH deficiency. Significant increases were observed in BMD after 1 year at the lumbar spine and after 1.5 years at the femoral neck. Serum total OC and carboxylated (c) OC increased and reached the maximum at 6 months, but the values remained over the baseline at both 12 and 18 months. The ucOC:total OC ratio changed contrarily: it decreased at 6 months, then increased again and reached the baseline level during the next 18 months. Serum calcium (Ca), phosphate (P) and total alkaline phosphatase (ALP) levels increased after 6 months, thereafter the Ca and P values decreased, while the total ALP remained elevated until 12 months. Serum parathormone decreased at 12 months and increased again thereafter. GH replacement therapy is associated with improvement of ucOC, a marker of fracture risk, which in addition to the increase of BMD, might contribute to the beneficial effect of GH replacement therapy on bone metabolism.

Adult↗

PubMed2000

[Effects of growth hormone replacement therapy in adults with severe growth hormone deficiency].

UNLABELLED: The aim of the study was to analyse the effects of GH replacement therapy (1 year duration) on body composition, carbohydrate metabolism, thyroid hormone metabolism and bone mineral density in 8 adults with growth hormone deficiency (5 women, 3 men; mean age 40 years). Mean maintenance dose of GH was 1.5 IU/day-1.76 IU/day for women and 1.07 IU/day for men, respectively--determined according to individual patient requirements. Serum insulin-like growth factor-I standard deviation score increased from -5.4 to 0.0 (p < 0.001). There was a significant negative relationship between serum insulin-like growth factor-I standard deviation score at the start of therapy and the increase in this score (r = -0.85; p < 0.05). The waist:hip ratio decreased after 12 months by 0.039 (p < 0.05). The glycosylated hemoglobin increased (4.43 +/- 0.56% vs. 5.86 +/- 0.27; p < 0.05), and a negative correlation of the baseline glycosylated hemoglobin to the glycosylated hemoglobin increase was found (r = -0.88; p < 0.01). Both the free triiodothyronine and free triiodothyronine:free thyroxine ratio increased (3.09 +/- 0.22 vs. 4.17 +/- 0.40; p < 0.05, and 0.234 +/- 0.02 vs. 0.324 +/- 0.04; p < 0.01), and a positive relationship was observed between this ratio at the start of therapy and the increase in the ratio (r = 0.76, p < 0.05). The bone mineral density of lumbar spine and femoral neck expressed as z-score increased (-1.18 +/- 0.56 vs. -0.75 +/- 0.48; p < 0.01 and -0.06 +/- 0.60 vs. 0.43 +/- 0.43; p < 0.05), while the bone mineral density of forearm was unchanged. CONCLUSIONS: Growth hormone replacement leads to a decrease in visceral fat, modulates the thyroid hormone levels by increasing peripheral conversion of thyroxine to triiodothyronine and probably is a physiological regulator of peripheral thyroxine metabolism, slightly deteriorates the carbohydrate metabolism, and results in an increase of bone mineral density of lumbar spine and femoral neck.

Adipose Tissue↗

PubMed2000

Changes of serum calcium level following thyroid surgery--reasons and clinical implications.

The reasons of transient hypocalcemia, frequently occurring after thyroid surgery, were investigated. Serum total calcium (seCa) and phosphorus (seP) levels were determined in 185 patients with benign nodular goiter before and after thyroid surgery. Beside these, in 27 additional patients, serum magnesium (seMg), total protein, albumin, calcitonin, parathormone (PTH) and 25-OH-D3 vitamin (25-OH-D3) levels were determined; corrected calcium (cCa) values, reflecting ionized calcium concentrations, were calculated. The daily changes of seCa and protein levels were measured in 20 patients. Another twenty patients, undergoing non-endocrinological surgery served as controls. Transient, mild but significant decrease of seCa was observed after surgery, while seP values were increased. Mild hypocalcemia (seCa<2.12 mmol/l) developed in 18.4%, severe hypo-calcemia (seCa<1.9 mmol/l) in 5.4% of the patients. The reduction of seCa levels was more pronounced in elderly, female patients. SeMg, total protein and albumin decreased, while cCa, PTH, calcitonin and 25-OH-D3 values did not change. Positive correlation was demonstrated between the change of seCa and albumin levels. Similar results were obtained in the general surgery group. In the thyroid operated group, in case of severe hypocalcemia, PTH levels decreased significantly into the pathological range. It may be concluded that transient, mild postoperative hypocalcemia is not a thyroid surgery-dependent phenomenon; it can also be observed after other operations accompanied by similar blood loss; in its development hypoalbuminemia plays a role. The causal role of PTH, calcitonin and 25-OH-D3 could not be proved in this study. Hypoparathyroidism can be responsible for the development of severe, prolonged hypocalcemia occurring at rare occasions.

Adolescent↗

PubMed1999

[The role of insulin-like-growth-factor-binding protein 3 in the evaluation of disease activity in acromegaly].

Studied the diagnostic value of measurements of insulin-like growth factor binding protein-3 compared to insulin-like growth factor-1 as a parameter of disease activity in patients with active (n = 12, 8 females, 4 males, 29-69 years old) and inactive (n = 14, 11 females, 3 males, 28-58 years old) acromegaly. Patients were assigned to the active group if they had GH levels > or = 2 ng/ml, to the inactive group if they had growth hormone levels < 2 ng/ml after 75 g glucose challenge. The absolute serum insulin-like growth factor-1 concentration (526 +/- 66 ng/ml vs. 272 +/- 61 ng/ml, p = 0.015; mean +/- SE) and the insulin-like growth factor-1 standard deviation score (3.23 +/- 0.33 vs. 0.67 +/- 0.58, p = 0.0013) was higher in the active than in the inactive group, but no significant difference was seen between the corresponding insulin-like growth factor binding protein-3 values (7270 +/- 1500 vs. 5340 +/- 1050 ng/ml). Positive significant correlation was found between insulin-like growth factor-1 and insulin-like growth factor binding protein-3 both in the active (n = 12, r = 0.55, p < 0.05) and in the inactive (n = 14, r = 0.61, p < 0.05) group. A significant negative correlation existed between insulin-like growth factor binding protein-3 and age in the inactive (r = 0.58, n = 14; p < 0.05), but not in the active (r = 0.35, n = 12) group. The diagnostic value of insulin-like growth factor binding protein-3 is less than that of the insulin-like growth factor-1. Conclude that the insulin-like growth factor binding protein-3 has smaller suitability to determine the activity of acromegaly than the insulin like-growth factor-1 measurement.

Acromegaly↗

PubMed1997

[Glycoprotein hormone alpha-subunit secretion in non-functioning pituitary adenomas].

The aim of the present study was to investigate the prevalence of elevated free glycoprotein hormone alpha-subunit in different pituitary adenomas, to establish the diagnostic value of the basal and stimulated free alpha-subunit secretion in non-functioning adenomas. Serum basal levels of alpha-subunit were increased in 1 of 22 untreated, in 1 of 16 operated patients with non-functioning adenoma, in 6 of 28 untreated, in 1 of 7 operated patients with acromegaly, in 0 of 5 untreated prolactinomas and in 0 of 1 untreated gonadotrop adenoma. Overall free alpha-subunit levels were increased in 9 of 79 cases (11.4%). In 6 of 9 patients with untreated non-functioning adenoma thyrotrop hormone releasing hormone caused an abnormal--paradox--elevation of serum alpha-subunit. These data indicate that measurement of basal and stimulated alpha-subunit is of relatively poor value in the diagnosis of non-functioning pituitary adenomas. The transsphenoidal surgery did not resulted in a change of alpha-subunit secretion neither in patients with non-functioning adenoma nor with acromegaly. The present data confirm the view that non-functioning pituitary adenomas are not homogeneous since this subset of tumors includes adenomas that either do not secrete measurable amounts of free alpha-subunit or produce normal or supranormal amounts of subunits as consequence of still undefined biosynthetic abnormalities.

Adenoma↗