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Biomedical subjects

M Haji

Publications and source records attributed to M Haji.

At least 73 records · Page 4Linked to original sources
PubMed1991

Atrial and brain natriuretic peptide in adrenal steroidogenesis.

We elucidated the role of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in human and bovine adrenocortical steroidogenesis. The urinary volume, sodium excretion and cyclic GMP (cGMP) excretion and plasma cGMP were markedly increased by the synthetic alpha-human ANP (alpha-hANP) infusion in healthy volunteers. Plasma arginine vasopressin (AVP) and aldosterone levels were significantly suppressed. Both ANP and BNP inhibited aldosterone, 19-OH-androstenedione, cortisol and DHEA secretion dose-dependently and increased the accumulation of intracellular cGMP in cultured human and bovine adrenal cells. alpha-hANP significantly suppressed P450scc-mRNA in cultured bovine adrenal cells stimulated by ACTH. Autoradiography and affinity labeling of [125I]hANP, and Scatchard plot demonstrated a specific ANP receptor in bovine and human adrenal glands. Purified ANP receptor from bovine adrenal glands identified two distinct types of ANP receptors, one is biologically active, the other is silent. A specific BNP receptor was also identified on the human and bovine adrenocortical cell membranes. The binding sites were displaced by unlabelled ANP as well as BNP. BNP showed an effect possibly via a receptor which may be shared with ANP. The mean basal plasma alpha-hANP level was 25 +/- 5 pg/ml in young men. We confirmed the presence of ANP and BNP in bovine and porcine adrenal medulla. Plasma or medullary ANP or BNP may directly modulate the adrenocortical steroidogenesis. We demonstrated that the lack of inhibitory effect of alpha-hANP on cultured aldosterone-producing adenoma (APA) cells was due to the decrease of ANP-specific receptor, which caused the loss of suppression of aldosterone and an increase in intracellular cGMP.

Adrenal Cortex↗
PubMed1991

Decreased expression of cytochrome P450 17 alpha-hydroxylase mRNA in senescent bovine adrenal gland.

To investigate the mechanisms of age-related decline in synthesis of adrenal androgen, we studied the contents of cortisol (F) and dehydroepiandrosterone (DHEA) and the amounts of cytochrome P450 17 alpha-hydroxylase (P450c17) mRNA and cytochrome P450 11 beta-hydroxylase (P450c11) mRNA in young (1 year old) and senescent (10-12 years old) bovine adrenal glands. We also examined effects of ACTH (10(-7) M) on the secretion of F and DHEA and on the induction of P450c17 and P450c11 mRNA expression in cultured adrenal cells from young and aged cows. The content of DHEA in adrenal glands and the secretion of DHEA in response to ACTH in cultured adrenal cells from senescent cow were lower than those from young cow, while the content and ACTH-stimulated secretion of F in senescent adrenals were of a similar level to those in young adrenals. The adrenal gland from aged cow showed a significantly lower level of P450c17 mRNA compared with young bovine adrenal. However, P450c11 mRNA was expressed in senescent adrenal glands at the same level as that in young adrenals. The induction of P450c17 mRNA by ACTH (10(-7) M for 24 h) in cultured adrenal cells from aged cow also showed a decline compared with that from young cow, although there was no difference the ACTH-induced accumulation of P450c11 mRNA in cultured adrenal cells between young and senescent cow. These results suggested that the expression of P450c17 mRNA decreased in aged bovine adrenal, which may cause the age-associated decline in biosynthesis of adrenal androgen.

Adrenal Glands↗
PubMed1991

Evidence for the secretion of inhibin-like immunoreactivity from cultured human adrenal cells.

We have studied the production and release of inhibin-like immunoreactivity in the human adrenal gland. Extract of human adrenal glands showed a displacement curve paralleled with the inhibin standard. Inhibin-like immunoreactivity contents in the adrenal gland was 1893 +/- 474 (mean +/- S.D.) IU/g wet weight tissue. ACTH stimulated the secretion of inhibin-like immunoreactivity as well as cortisol and aldosterone in a dose-dependent manner in the cultured adrenal cells. These results indicate that the human adrenal gland produces and secretes inhibin-like peptide in response to ACTH.

Adrenal Glands↗
PubMed1990

Production of immunoreactive inhibin by a virilizing ovarian tumour (Sertoli-Leydig tumour).

A 59-year-old post-menopausal woman was admitted to the hospital with atypical vaginal bleeding and hirsute lower extremities. There was a high serum testosterone level (15.8 nmol/l) and also an appreciable serum immunoreactive inhibin level. No adrenal or ovarian lesions were detected by conventional imaging procedures. Selective blood sampling was performed during venous catheterization and showed that testosterone and inhibin levels were highest in the right ovarian vein. Laparotomy revealed a Sertoli-Leydig tumour in the right ovary, which was excised. Post-operatively, immunoreactive inhibin became undetectable while the testosterone level fell to 2.8 nmol/l. Specific radioimmunoassay showed a high immunoreactive inhibin content in the tumour. These findings indicate that Sertoli-Leydig tumours can produce both testosterone and immunoreactive inhibin, both of which would then inhibit LH and FSH release to produce the symptoms seen in this patient. Thus, assay of inhibin may aid in the differential diagnosis of virilizing tumours.

Female↗
PubMed1990

Expression of c-fos and c-myc proto-oncogenes in human adrenal pheochromocytomas.

We examined c-fos and c-myc expressions in pheochromocytoma tissues from six patients. All samples contained c-fos and c-myc transcripts, whereas mRNA from bovine adrenal medulla, as a control, did not contain these transcripts at detectable levels. Southern blot analysis revealed no amplification and no rearrangement of c-fos and c-myc genes. We also examined the gene expression of insulin-like growth factor-II (IGF-II), a mitogen for rat pheochromocytoma cells exerted by autocrine or paracrine fashion. All samples from the pheochromocytomas contained IGF-II transcripts as well as c-fos and c-myc transcripts. The constitutive expressions of c-fos and c-myc genes may be interpreted to mean that pheochromocytoma is in a state of growth stimulation in vivo by growth factors, including IGF-II.

Adrenal Gland Neoplasms↗
PubMed1990

Decreased levels of steroid 21-hydroxylase [P450(c21)] and its mRNA in an adrenocortical adenoma associated with 21-hydroxylase deficiency.

Adrenocortical adenoma incidentally found in a 37-yr-old female patient, with simple virilizing form of 21-hydroxylase deficiency, was studied. Cultured adenoma cells revealed excessive secretion of 17 alpha-hydroxyprogesterone in response to 10(-8) M ACTH, compared with those of 11-deoxycortisol and cortisol, which indicated impaired activity of the 21-hydroxylase. To elucidate the molecular mechanisms of this defective 21-hydroxylase in the adenoma, we analyzed the gene encoding specific cytochrome P450 (P450c21) for steroid 21-hydroxylation and its expression. DNA and RNA were extracted from the adrenal adenoma and were hybridized with a probe of human P450c21 gene, by Southern and Northern blot analysis. In Southern blot analysis with Taq I, Bgl II or Bam HI, there was no difference between the pattern of restriction fragments in DNA from the adenoma and normal peripheral leucocytes. Northern blot analysis of the adenoma showed the same size of P450c21 mRNA as in the normal adrenal gland, but the amount was low--about a half that of the normal adrenal. In Western blot analysis with polyclonal antibody to P450c21, only a small amount of P450c21 protein was detected in the adenoma, although it was found to be of the same molecular weight as that in the normal adrenal gland. In view of these findings it is conceivable as one of possibilities that a mild and small mutation in the structural or promotor region of the P450c21 gene may cause the decreased 21-hydroxylase activity in this adenoma.

Adenoma↗
PubMed1990

[A case of hypopituitarism associated with empty sella and agenesis of corpus callosum, a variant form of septo-optic-pituitary dysplasia].

A 41-year-old man was referred to Kyushu University Hospital for evaluation of hypothyroidism and hypocortisolemia. Pituitary function test revealed the deficiency of GH(growth hormone), ACTH(adrenocorticotropic hormone), prolactin and TSH(thyroid stimulating hormone). MRI showed empty sella and agenesis of corpus callosum. Clinical diagnosis was hypopituitarism with midline brain anomaly. Septo-optic-pituitary dysplasia (SOPD) is a syndrome characterized by agenesis of septum pellucidum or corpus callosum, optic nerve hypoplasia and congenital hypothalamic-pituitary insufficiency. Our case had no ocular anomalies, but today it is regarded as a variant form of SOPD. Evaluation of the integrity of midline brain structures in patients with congenital hypopituitarism is thus thought to be important for their etiology.

Adult↗
PubMed1990

[Structure and function of the receptor for human atrial natriuretic peptide in cultured human skin fibroblasts].

Cultured human skin fibroblasts possessed the high-affinity and low-capacity binding sites for [125I]alpha-human atrial natriuretic peptide (hANP), in which the dissociation constant and maximal binding capacity were computed to 68.7 +/- 11.3 pM and 7.3 +/- 1.2 fmols/mg protein, respectively, from Scatchard plot analysis. The specific [125I] alpha-hANP binding sites of cultured human fibroblast were displaced by unlabeled atriopeptin I, a truncated analogue, to the same extent as the case of alpha-hANP. In human adrenal membrane fractions, [125I] alpha-hANP binding sites were suppressed only by unlabeled alpha-hANP, while the high concentrations of atriopeptin I could slightly inhibit the binding sites for alpha-hANP. As it was reported that atriopeptin I had more significant affinity to the low-molecular weight ANP receptor (60-70 KD) than that to the high-molecular weight form (130-140 KD), the specific bindings may be attributed by the low-molecular weight ANP receptor in cultured human fibroblasts. Furthermore, alpha-hANP up to 10(-8)M failed to induce the significant cGMP formation in cultured human skin fibroblasts. The molecular weight of [125I]alpha-hANP binding sites of human fibroblasts was identified only at the region of 67 KD and no radioactive band was visualized around the region of large molecular weight ANP receptor in the SDS gel electrophoresis of a crosslinked [125I]alpha-hANP-receptor complex. In contrast, the affinity labeling of [125I]alpha-hANP to the human adrenal membrane fractions showed that 135 KD binding sites were responsible to the human adrenal ANP receptor. In conclusion, cultured human skin fibroblasts have a high-affinity low-capacity receptor for ANP. The molecular weight of ANP receptor is approximately 67 KD, and ANP-specific guanylate cyclase may not be linked to the receptor, suggestive that so-called C receptor may be localized in cultured human fibroblasts.

Adrenal Glands↗
PubMed1989

Porcine brain natriuretic peptide receptor in bovine adrenal cortex.

The action of porcine brain natriuretic peptide (pBNP) on the steroidogenesis was investigated in cultured bovine adrenocortical cells. Porcine BNP induced a significant dose-dependent inhibition of both ACTH- and A II-stimulated aldosterone secretion. 10(-8) M and 10(-7) M pBNP also significantly inhibited ACTH-stimulated cortisol and dehydroepiandrosterone (DHEA) secretions. Binding studies of [125I]-pBNP to bovine adrenocortical membrane fractions showed that adrenal cortex had high-affinity and low-capacity pBNP binding sites, with a dissociation constant (Kd) of 1.70 x 10(-10) M and a maximal binding capacity (Bmax) of 19.9 fmol/mg protein. Finally, the 135 Kd radioactive band was specially visualized in the affinity labeling of bovine adrenal cortex with disuccinimidyl suberate (DSS). These results suggest that pBNP may have receptor-mediated suppressive actions on bovine adrenal steroidogenesis, similar to that in atrial natriuretic peptide (ANP).

Adrenal Cortex↗
PubMed1989

Serum fructosamine in assessment of diabetic control and relation to thyroid function.

Measurement of serum fructosamine using a Roche kit is a simple and reliable method for the estimation of glycated serum proteins. The value of serum fructosamine can be affected by hyperglycemia in diabetics and an abnormal turnover rate of serum protein in patients with thyroid dysfunction. We measured the serum fructosamine level in 18 normal control subjects, 71 diabetics (8 IDDM, 63 NIDDM) and 46 non-diabetic untreated patients with thyroid dysfunction (28 hyperthyroidism, 18 hypothyroidism). The serum fructosamine level was significantly increased in the diabetics compared with the normal control subjects (3.84 +/- 0.15 mmol/l vs 2.58 +/- 0.08; mean +/- SE, P less than 0.01). The serum fructosamine level in the diabetics was positively correlated with the fasting plasma glucose and HbAlc level, showing the highest correlation with fasting plasma glucose at 2 weeks before and with the HbAlc level at 2 weeks after serum fructosamine measurement. In the patients with thyroid dysfunction, the serum fructosamine level in hyperthyroidism (2.08 +/- 0.03 mmol/l) and hypothyroidism (3.11 +/- 0.07 mmol/l) were significantly lower (P less than 0.001) and higher (P less than 0.001) than the normal control subjects (2.58 +/- 0.08 mmol/l), respectively. Furthermore, the serum fructosamine level in these patients was negatively correlated with the level of serum thyroid hormones such as T3 (P less than 0.001) and T4 (P less than 0.001). It is concluded that measurement of serum fructosamine is clinically useful for the evaluation of shorter-term glycemic control in diabetics, but its level for diabetic patients with thyroid dysfunction must be cautiously interpreted.

Adult↗
PubMed1989

Growth hormone releasing hormone-sensitive adenylate cyclase activity in growth hormone-producing pituitary adenoma: correlation to the response of plasma growth hormone to growth hormone releasing hormone in patients with acromegaly.

The correlation between response of plasma GH to GHRH and the GHRH-induced stimulation of the intracellular adenylate cyclase (AC) activity in pituitary adenoma cell membranes in acromegalic patients was investigated. Each peak plasma GH level after iv administration of GHRH ranged from 1.1 to 13.8 times the basal level in 13 acromegalic patients. On the other hand, the maximal stimulation of intracellular AC activity (cAMP production) induced by GHRH varied from 1.4 to 6.4 times the control level in each GH-producing pituitary adenoma cell membrane. A significant positive correlation (r = 0.89, P less than 0.005) between plasma GH response to GHRH and intracellular cAMP production stimulated by GHRH was observed in nine of the acromegalic patients. In contrast, the response of plasma GH to GHRH was significantly blunted, despite a fairly large production of intracellular cAMP stimulated by GHRH, in the other four acromegalic patients. These results suggest that GHRH-induced GH release from GH-producing pituitary adenomas of patients with acromegaly may be regulated not only by GHRH receptor-adenylate cyclase system but also modified by several other factors including somatostatin and Sm-C.

Acromegaly↗
PubMed1989

Evidence for age-related change in plasma 19-hydroxyandrostenedione.

The steroid, 19-hydroxyandrost-4-ene-3, 17-dione (19-hydroxyandrostene-dione, 19-OH-A-dione) has been known to enhance the mineralocorticoid action of aldosterone. To investigate the age-related change in the plasma 19-OH-A-dione concentration, plasma 19-OH-A-dione, androst-4-ene-3, 17-dione (A-dione), aldosterone and cortisol of 38 non-hypertensive healthy subjects (18 young men and 20 aged men) measured by specific radioimmunoassays. The basal plasma 19-OH-A-dione and A-dione concentration in aged men was significantly lower than in young men (P less than 0.01). Moreover, there was found to be a positive correlation between plasma 19-OH-A-dione and A-dione (P less than 0.01). On the other hand, plasma aldosterone and cortisol in aged men showed a tendency to decrease, but no statistical significance compared to young men was observed. This study demonstrated that there was an apparent age-related decrease not only in plasma A-dione, but also in plasma 19-OH-A-dione, an amplifier or aldosterone action.

Adolescent↗
PubMed1988

Adrenocortical tumor in a patient with untreated congenital adrenocortical hyperplasia owing to 21-hydroxylase deficiency: characterization of steroidogenic lesions.

We report a case of congenital adrenal hyperplasia complicated by a right adrenal adenoma. The congenital adrenal hyperplasia was confirmed by extremely high levels of basal serum 17 alpha-hydroxy-progesterone and urinary pregnantriol as well as an exaggerated response of 17 alpha-hydroxyprogesterone to adrenocorticotropic hormone. On roentogenographic examinations and an echogram a huge calcified tumor was seen in the right adrenal gland. Histological findings indicated an adrenocortical adenoma. Culture of the tumor cells showed an accentuated response in the ratio of 17 alpha-hydroxy-progesterone to desoxycortisol with adrenocorticotropic hormone as a stimulator, suggesting that such adenoma cells also lack 21-hydroxylase activity. Our study clearly demonstrates that tumor cells have the same steroidogenic lesions as hyperplasia.

Adenoma↗
PubMed1988

Age-related changes in glucocorticoid and androgen receptors of cultured human pubic skin fibroblasts.

In order to evaluate age-related changes in glucocorticoid receptor and androgen receptor of cultured human pubic skin fibroblasts in young and aged men, we determined both [3H]dexamethasone binding and [3H]methyltrienolone (R1881, potent androgenic steroid) binding, using dispersed whole cell assay. Scatchard analyses of specific [3H]dexamethasone binding to the fibroblasts of young and aged men showed a single class of high-affinity binding sites with a mean (+/- SD) binding site concentration (Bmax) of 12.69 +/- 2.36 X 10(4) and 12.87 +/- 12.21 X 10(4) sites/cell, respectively, and mean (+/- SD) dissociation constant (Kd) of 5.60 +/- 0.41 and 7.36 +/- 2.17 nM, respectively. Scatchard analyses of specific [3H]R1881 binding to the same cultured skin fibroblasts of young and aged men showed a single class of high-affinity binding sites with a mean Bmax of 5.77 +/- 1.02 X 10(3) and 2.82 +/- 0.97 X 10(3) sites/cell, respectively, and a mean Kd of 0.56 +/- 0.23 and 0.50 +/- 0.28 nM, respectively. These findings indicate that there were no significant age-related changes in binding site and affinity of glucocorticoid receptor in cultured human pubic skin fibroblasts, whereas binding sites of androgen receptor significantly decreased in those of aged men as compared to young men, without significant change in affinity.

Adult↗
PubMed1988

A case of glucocorticoid-suppressible hyperaldosteronism with aldosterone producing adenoma.

A 34-yr-old woman with hypertension (142/102 mmHg), hypokalemia, high plasma and urinary aldosterone and low plasma renin activity was studied. A left adrenal tumor and enlarged right adrenal gland were demonstrated by adrenal venography. During administration of dexamethasone (2 mg daily, for 3 weeks), urinary aldosterone excretion decreased abruptly from 22.5 to 9-11 micrograms/day, serum potassium increased and blood pressure fell to 120-130/80-90 mmHg. After left adrenalectomy, all manifestations improved with no medication. The resected adrenal gland revealed clear cell adenoma and micronodular adrenocortical hyperplasia. The patient was considered to be a rare case of glucocorticoid-suppressible hyperaldosteronism with an aldosterone-producing adenoma.

Adenoma↗
PubMed1987

Preproenkephalin A-derived opioid peptides and mRNA of preproenkephalin A in human pheochromocytomas.

Tissue contents of immunoreactive met-enkephalin (Met-Enk), leu-enkephalin (Leu-Enk) and met-enkephalin-Arg-Gly-Leu (Met-Enk-AGL) were determined by specific RIAs in 17 pheochromocytomas and the levels of preproenkephalin A mRNA were compared in some of these tissues by Northern blot hybridization. Remarkably wide distributions in the amounts of immunoreactive Met-Enk, Leu-Enk and Met-Enk-AGL were observed in 17 pheochromocytomas. Medullary pheochromocytomas contained significantly larger amounts of immunoreactive Met-Enk, Leu-Enk and Met-Enk-AGL than did the extramedullary ones. Significant positive correlations of tumor tissue immunoreactivities between Met-Enk and Leu-Enk (r = 0.97, P less than 0.01) and between Met-Enk and Met-Enk-AGL (r = 0.97, P less than 0.01) were observed. No difference in size of mRNA of preproenkephalin A was observed in the pheochromocytomas. Medullary pheochromocytomas contained higher amounts of preproenkephalin A mRA than did the extramedullary ones. The quantities of preproenkephalin A mRNA in nine pheochromocytoma tissues significantly correlated with those of immunoreactive Met-Enk in these tissues (r = 0.94, P less than 0.01). These results indicate that the remarkable difference in tissue immunoreactivities of preproenkephalin A-derived opioid peptides is decided at the transcriptional level but not at the posttranslational level.

Adrenal Gland Neoplasms↗