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Biomedical subjects

R Oosterom

Publications and source records attributed to R Oosterom.

At least 55 records · Page 3Linked to original sources
PubMed1984

A close correlation between the amount of met-enkephalin-immunoreactivity and epinephrine in adrenal pheochromocytoma tissue from patients with Sipple's syndrome.

The concentration of epinephrine, norepinephrine, dopamine, met-enkephalin-, ACTH-, calcitonin- and somatostatin-like immunoreactivity (IR) were determined in the extracts of 9 adrenal pheochromocytomas from 7 patients. Six of these patients had Sipple's syndrome. There was a close correlation between the amounts of met-enkephalin-IR and of epinephrine present in the tumor tissue (p less than 0.01). Such a correlation was not found between catecholamines and the other polypeptide hormones investigated. The relevance of the close parallel in the occurrence of met-enkephalin-IR and epinephrine in human adrenal pheochromocytoma tissue is unknown, but it underlines earlier observations in the normal bovine and rat adrenal medulla on a co-storage and co-release of these substances in normal circumstances.

Adolescent↗
PubMed1984

Isolation of large numbers of dispersed human pituitary adenoma cells obtained by aspiration.

Since the extent of in vitro experiments with human pituitary adenoma cells is often limited by the small number of cells isolated from surgical specimens, ways to obtain more cells are of interest. In this study we made use of tumor tissue removed by aspiration through a suction tube during transsphenoidal surgery. Fifteen out of 28 adenomas could be dispersed without enzymatic treatment. The other 13 adenomas were mildly treated with Dispase. The large number of red blood cells present in the suction tube were removed by Ficoll-Isopaque density centrifugation. More than 90% of the adenoma cells were recovered from the interphase fraction. This material, in contrast with fragments obtained with a forceps, yielded 35.9 (+/-9.0) X 10(6) cells (mean +/- SE, n = 28). Usually less than 10% of these cells were mononuclear leucocytes. Pituitary hormones other than those hypersecreted in vivo were not found in the incubation media; only small amounts of LH were found in 5 out of 25 adenomas. A linear relationship was found between cell concentration and hormone secretion, both for PRL and GH. In vitro hormone secretion by the adenoma cells was in good agreement with in vivo dynamic tests. In longterm culture, GH and ACTH secretion by the adenoma cells declined, while PRL secretion was fairly constant. It is concluded that large numbers of dispersed pituitary adenoma cells can be obtained from the material removed by suction during transsphenoidal operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1984

Regulation of hormone release by cultured cells from a thyrotropin-growth hormone-secreting pituitary tumor. Direct inhibiting effects of 3,5,3'-triiodothyronine and dexamethasone on thyrotropin secretion.

The regulation of TSH and GH secretion was investigated in cultured tumor cells prepared from a mixed TSH/GH secreting pituitary tumor. The tumor tissue had been removed transsphenoidally from a patient with hyperthyroidism and inappropriately high serum TSH levels and acromegaly. TSH and GH secretion by cultured cells were stimulated in a parallel way by TRH (300 nM) and LHRH (50 nM), but were unaffected by bromocriptine (10 nM). Exposure of the tumor cells to dexamethasone (0.1 microM) or T3 (50 nM) had differential effects on hormone secretion. GH secretion was greatly stimulated by dexamethasone, but unaffected by T3. TSH secretion was inhibited both by T3 and by dexamethasone. So, T3 and glucocorticoids inhibit TSH release by the human pituitary tumor cells studied at least partly by means of a direct effect.

Acromegaly↗
PubMed1984

Mechanism of action and tolerance of mesulergine.

The tolerance and prolactin (PRL) release-inhibiting action of the 8 alpha-aminoergoline, mesurlergine, were investigated. In a blind crossover study in six subjects with hyperprolactinemia, 0.5 mg mesulergine induced fewer side effects than did 2.5 mg bromocriptine, while the PRL release-inhibiting effect of the two was of the same order. Six different subjects with suspected PRL-secreting pituitary adenomas who (repeatedly) had to discontinue bromocriptine because of nausea, vomiting, or symptoms of orthostatic hypotension were treated for 20 mo with mesulergine (1 to 2 mg/day). Mesulergine did not induce side effects and its actions resembled those of bromocriptine. Mesulergine induced cessation of galactorrhea and resumption of normal menstrual cycles in five subjects, while in one subject an insufficient luteal phase persisted. No abnormalities in routine blood parameter estimations were observed. In two of three subjects there was shrinkage of a pituitary tumor after 12 to 15 mo on mesulergine. Mesulergine did not directly inhibit PRL release by cultured normal rat pituitary cells and human prolactinoma cells and it antagonized the action of dopamine in a dose-dependent manner. This suggests that the dopaminergic action is carried out by a metabolite of mesulergine, while the parent drug probably prevents the well-known side effects of dopamine-agonistic drugs by its dopamine receptor blocking activity. Because of its acceptability, mesulergine might be important in the treatment of hyperprolactinemia and perhaps also of acromegaly and Parkinson's disease.

Adenoma↗
PubMed1984

Hyperprolactinemia exerts a negative effect on the beta-endorphin content of the rat neurointermediate pituitary lobe.

Implantation of the PRL, ACTH, beta-endorphin (beta-EP), and beta-lipotropin (beta-LPH)-secreting transplantable rat pituitary tumor 7315a resulted in a suppression of the PRL and the ACTH content of the anterior pituitary gland and also of the beta-EP/beta-LPH content of the neurointermediate (NI) lobe. Treatment with bromocriptine further diminished the anterior lobe PRL content, whereas haloperidol partially inhibited this tumor-mediated diminution. The administration of these drugs did not influence the suppressed ACTH content of the anterior pituitary lobe. The diminished beta-EP/beta-LPH content of the NI lobe of tumor-bearing rats became completely normal after treatment with haloperidol, whereas bromocriptine administration further diminished the NI lobe beta-EP/beta-LPH content. There was a close correlation between the anterior pituitary lobe PRL content and the beta-EP/beta-LPH content of the NI lobe in all four groups of rats taken together (including nontumor-bearing controls, control tumor rats, and tumor rats treated with bromocriptine or haloperidol; P less than 0.01). Implantation of the pure PRL-secreting pituitary tumor 7315b resulted in hyperprolactinemia and a suppression of the PRL content of the anterior lobe and the beta-EP/beta-LPH content of the NI lobe, without affecting the ACTH content of the anterior pituitary lobe. There was a negative correlation between the level of the circulating PRL concentration and the beta-EP/beta-LPH content of the NI lobe. These results suggest a possible relationship between the synthesis of PRL by the anterior pituitary lactotroph and of the hormones of the NI lobe. The level of the circulating PRL concentration may play, directly or indirectly, a role in the regulation of both systems.

Adrenocorticotropic Hormone↗
PubMed1984

The interrelationship between the effects of somatostatin and human pancreatic growth hormone-releasing factor on growth hormone release by cultured pituitary tumor cells from patients with acromegaly.

The effects of somatostatin (SRIF) and human pancreatic tumor GRF on GH release by cultured pituitary tumor cells obtained during transsphenoidal operation from 15 acromegalic patients were investigated. In a study of the sensitivity of pathological GH release to SRIF, 1-10 nM SRIF induced maximal inhibition of hormone release in 3 consecutive tumors. In 12 of 15 tumor cell cultures, 10 nM SRIF produced statistically significant inhibition of basal GH release by 39 +/- 3% (mean +/- SEM). In 2 of the 3 other tumors, SRIF inhibited GRF-stimulated GH release, while this was not investigated in the third tumor. A dose-response study of the effect of GRF on GH release by cultured pituitary tumor cells showed that doses of 0.1, 1, 10, and 100 nM induced similar maximal (35%) stimulation of hormone secretion. In four of five consecutive tumor cell suspensions, 1 and 10 nM GRF induced statistically significant GH stimulation by 18-300%. Preincubation of the tumor cells with 5 nM dexamethasone greatly increased the sensitivity and the maximal stimulation in response to GRF and made one tumor cell suspension, which did not react to GRF initially, sensitive to GRF. In the tumors of four patients, the interrelationship between the effects of SRIF and GRF on GH release were also studied. SRIF (10 nM) inhibited the stimulatory effects of GRF on GH release virtually completely. In conclusion, GH release by in vitro cell cultures of GH-secreting pituitary adenomas was inhibited by SRIF and stimulated by GRF. The interaction of GRF and SRIF on GH release by these pituitary tumor cells was similar to that in normal rat GH cells, as SRIF virtually completely overcame the GRF-induced GH release.

Acromegaly↗
PubMed1984

Corticotropin-releasing factor (ovine) and vasopressin exert a synergistic effect on adrenocorticotropin release in man.

The effects of ovine CRF, lysine vasopressin (LVP), and their interrelationships, and rat hypothalamic extract (HME), on ACTH and beta-endorphin release by human pituitary tumor cells from two patients with Nelson's syndrome and one with Cushing's disease and on ACTH and cortisol secretion in vivo were studied. In cultured pituitary tumor cells, both LVP and CRF greatly stimulated ACTH and beta-endorphin release at maximally active concentrations of 0.1 microM and 10 nM, respectively. At these concentrations, the combination of the two substances had an additive or synergistic effect on hormone release. Low concentrations of HME potentiated and/or were synergistic with CRF-mediated ACTH release. In vivo, the combination of CRF (1 microgram/kg) and LVP (10 pressor units) induced greater ACTH release than the sum of the responses to CRF and LVP alone. This synergistic effect of CRF plus LVP concerned only ACTH release, while cortisol release after CRF plus LVP was equivalent to the sum of the maximal increments in this hormone after CRF and LVP alone. The peak levels of cortisol after a combination of CRF and LVP probably reflect the maximum stimulatory capacity of the adrenal cortex. These data support the concept that in man, both ovine CRF and vasopressin are corticotropin-releasing factors which act synergistically. Both substances might well regulate, at the pituitary level, the responsiveness of the pituitary-adrenal axis to stimuli reaching the hypothalamus. A test using ovine CRF and LVP together might provide a better index of total pituitary ACTH reserve than one using the two compounds separately.

Adrenocorticotropic Hormone↗
PubMed1984

ACTH and beta-endorphin secretion by three corticotrophic adenomas in culture. Effects of culture time, dexamethasone, vasopressin and synthetic corticotrophin releasing factor.

Dispersed corticotrophic cells of 3 patients with Nelson's syndrome were studied in tissue culture for up to 25 days. During this culture period a parallel decrease with time was seen in ACTH and beta-endorphin-like immunoreactivity ( LIR ) release. A concomitant decline was observed for intracellular hormones. The time course of hormone release showed a parallel secretion of ACTH and beta-endorphin- LIR up to 8 h. Both the release of ACTH and beta-endorphin LIR were stimulated by 0.1 microM lysine vasopressin (LVP) in all three adenoma cell cultures. Dexamethasone (0.1 and 1 microM) suppressed basal hormone secretion for 4 h. Synthetic ovine corticotrophin-releasing factor (CRF) at 10 and 100 nM stimulated the secretion of ACTH and beta-endorphin LIR maximally. This stimulation was higher than observed with maximal stimulative concentration of LVP (0.3 microM). The CRF-mediated hormone secretion was calcium-dependent. Dexamethasone (0.1 microM) blocked the stimulating effect of 10 nM CRF completely. Gel-filtration chromatography demonstrated the cells to secrete both beta-lipotrophin (beta-LPH) and beta-endorphin. The ratio of beta-LPH to beta-endorphin released remained constant upon stimulation by LVP and CRF. HPLC studies demonstrate the possibility that several beta-endorphin fragments, including alpha-endorphin and gamma-endorphin, were secreted by cells from a Nelson tumour. CRF caused a simultaneous parallel stimulation of the release of these peptides.

Adenoma↗
PubMed1984

Human growth hormone-secreting pituitary adenoma cells in long-term culture: effects of dexamethasone and growth hormone releasing factor.

Growth hormone-secreting human pituitary adenoma cells in long-term culture show a decline in GH secretion. We investigated the effects of dexamethasone on GH production and on the responsiveness of the adenoma cells to various drugs. Twenty-four-hour GH secretion by cultures from seven acromegalics was consistently stimulated by 100 nM-dexamethasone. In four out of seven cultures the effect of dexamethasone occurred within 24 h. After 3 weeks in culture the decline in GH secretion by control cultures was over 90%, while in dexamethasone-treated cultures this was limited to less than 50%. The effect of dexamethasone was dose-dependent over a range of 1 nmol/l to 10 mumol/l. Dexamethasone stimulated not only GH secretion (fivefold), but also GH content (twofold). Cycloheximide and actinomycin D blocked the stimulatory effect of dexamethasone on GH secretion, the latter irreversibly. After 4 days of treatment with 100 nM-dexamethasone, the relative effects of somatostatin, prostaglandin E1, bromocriptine and thyrotrophin releasing hormone were the same in treated and untreated cultures. However, the response to synthetic GH releasing factor (GRF) was greatly enhanced by pretreatment of adenoma cells with dexamethasone (100 and 5 nmol/l). Cells unresponsive to small concentrations of GRF could be stimulated effectively by GRF after pretreatment with dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1983

Relationship between cytological picture and hormone secretion by human pituitary adenomas in cell culture.

In 22 endocrinologically active hypophyseal adenomas the relationship between the biological behaviour and the cytological picture was investigated. There was a positive correlation between the atypia of the cells in the cytograms and hormone secretion of the tumour cells in vitro and the clinical aggressiveness. Cytological examination gave a better insight into the biological properties of these tumours than histological methods.

Adenoma↗
PubMed1983

Basal and dopamine-inhibited prolactin secretion by rat anterior pituitary cells: effects of culture conditions.

Culture conditions for rat pituitary cells were investigated which would result in high PRL synthesis and secretion with maintenance of dopamine-mediated inhibition of PRL secretion. From five commercially available media, RPMI resulted in the highest PRL content and secretion, but no inhibition of PRL secretion by dopamine was observed. MEM with Earle's salts fulfilled best our requirements for culturing functional PRL-secreting cells. PRL secretion was not affected by variations in the concentration of fetal calf serum, but was positively correlated with increasing horse serum concentrations. TRH-induced PRL release increased with increasing serum concentrations and was positively correlated with the concentration of 17 beta-estradiol in the culture medium (P less than 0.0025). An increase in the sodium bicarbonate concentration from 0.85 to 3.0 g/l resulted in a 4-fold stimulation of PRL synthesis and in a 27-fold stimulation of PRL secretion. However, at bicarbonate concentrations above 2.6 g/l, inhibition of PRL secretion by 500 nM dopamine was lost. The addition of 20 mM Hepes to the culture medium decreased basal PRL secretion by 48 +/- 13% (P less than 0.01), while dopamine inhibition of PRL secretion was reduced from 49 +/- 10% to 24 +/- 8% (P less than 0.05). When an increasing number of pituitary cells was cultured in a constant volume, PRL secretion expressed per cell increased up to 0.3-0.4 X 10(6) cells/dish/2 ml. With higher cell concentrations of up to 1 X 10(6) cells/dish, PRL secretion per cell diminished significantly, which indicates a direct negative feedback of high medium PRL on the PRL-secreting pituitary cells. In this culture system dopamine inhibited PRL secretion over a 4 h period in a dose-dependent manner (IC50 20 nM), while no paradoxical stimulation of PRL secretion was observed with low dopamine concentrations. However, a 25% stimulation (P less than 0.05) of PRL secretion by 0.1 nM dopamine could be obtained by addition of 0.01% ascorbic acid, which by itself decreased basal PRL secretion by 49% (P less than 0.01). Thus, tissue culture conditions that result in high PRL production are not necessarily the best choice, since dopamine-mediated inhibition of PRL secretion is another important parameter for the functioning of lactotrophs in culture. The best compromise is MEM with 2.2 g/l of sodium bicarbonate, without Hepes buffer and supplemented with 10% FCS.

Animals↗
PubMed1983

Transplantation of human pituitary adenomas into nude mice.

In vitro studies with human pituitary adenomas are limited by the small amount of tissue obtained, which may be contaminated by the surrounding normal pituitary tissue. In this study we investigated if the passage of adenoma tissue via thymusless nude mice could solve some of these problems. The secretory capacity of the transplanted human pituitary adenomas was demonstrated by the presence of hGH and/or hPRL in the plasma of the host mouse, while other human pituitary hormones (TSH, LH and FSH) were undetectable. The transplants, however, decreased in size with time although histologically viable adenoma tissue was recovered that resembled the original tumor. Upon trypsinization of the small tissue fragments no viable adenoma cells could be obtained. In contrast, an experimental malignant rat pituitary tumor grew steadily with time, resulting in high levels of rPRL in the nude mice recipients. Large numbers of viable tumor cells were recovered from these tumors. Thus, human pituitary adenomas transplanted in nude mice continue to release hormone(s), but the transplants decrease in size and cannot be used to isolate dispersed tumor cells for in vitro studies.

Adenoma↗
PubMed1983

Growth hormone secretion by cultured rat anterior pituitary cells. Effects of culture conditions and dexamethasone.

Optimal conditions were sought for the study of GH secretion by cultured normal pituitary cells. Dispersed rat pituitary cells were cultured for 1 week in four different media supplemented with 10% fetal calf serum. Minimal essential medium resulted in high GH content and secretion during a 4-h incubation period, whereas GH secretion was lower (P less than 0.05) for cells cultured in medium 199, Ham's F-10, and RPMI-1640. GH secretion/24 h declined gradually with time. After 2 weeks in culture hormone secretion amounted to 30% of secretion on day 1, but after 3 weeks GH secretion was still measurable. GH recovery during the 3-weeks culture period was more than 600% of the amount initially plated. GH secretion was positively correlated with the bicarbonate concentration between 0.85 and 2.2 g/liter NaHCO3. When pituitary cells were cultured in concentrations varying from 0.5 X 10(5) to 10 X 10(5) cells per dish, GH secretion and content per cell were constant, suggesting that no direct autofeedback occurred in cultures with high cell densities and thus high medium GH. Dexamethasone stimulated GH secretion and content in a dose-dependent way (0.1 nM-10 microM). The stimulatory effect of 100 nM dexamethasone occurred within 24-48 h. After 7 days of treatment with 100 nM dexamethasone, GH secretion had increased to 190% and GH content to 230% of control. In contrast to the effects on GH, dexamethasone suppressed PRL secretion in a dose-dependent way, but this effect was seen only after 7 days of treatment and not after 4 days of treatment. Cycloheximide and actinomycin D prevented the stimulatory effect of dexamethasone on GH secretion. However, 24 h after cessation of cycloheximide treatment GH secretion was stimulated by dexamethasone. Four days of treatment with 100 nM dexamethasone did not affect the GH response to somatostatin, prostaglandin E1, and theophylline, nor the PRL response to dopamine, TRH, and theophylline. Thus, culture conditions may affect GH production, and dexamethasone can be used to culture somatotrophs for longer periods with steady GH production and normal responsiveness.

Alprostadil↗
PubMed1983

Absence of a suppressive effect of 2-hydroxyestrone on hyperprolactinemia in patients with prolactinomas before and after estradiol administration.

The effect of the infusion of 2-hydroxyestrone (125 micrograms/h for 8 h) on plasma PRL levels was investigated before and 64 h after the administration of 1 mg estradiol benzoate in five patients with PRL-secreting pituitary adenomas. There was no effect on the circulating PRL levels measured hourly for 8 h during both episodes of 2-hydroxyestrone infusion, but plasma LH and FSH levels were suppressed. Infusion of 2-hydroxyestrone in two hyperprolactinemic patients with craniopharyngeomas also did not change the circulating PRL levels. We conclude that: 1) 2-Hydroxyestrone does not suppress PRL levels in patients with prolactinomas. This is not caused by the low estrogenic state of these patients, because 2-hydroxyestrone remained ineffective after the administration of estradiol. 2-Hydroxyestrone was also not able to suppress the estradiol-induced stimulation of PRL release. 2) 2-Hydroxyestrone does not diminish PRL levels in patients with suprasellar tumors and hyperprolactinemia. Therefore, infusion of 2-hydroxyestrone cannot be used in the differential diagnosis of hypothalamic and tumoral hyperprolactinemia.

Adult↗
PubMed1983

Effect of cyproheptadine, desmethylcyproheptadine, gamma-amino-butyric acid and sodium valproate on adrenocorticotrophin secretion by cultured pituitary tumour cells from three patients with Nelson's syndrome.

The effects of cyproheptadine, desmethylcyproheptadine, serotonin, gamma-amino-butyric acid (GABA) and sodium valproate were studied on ACTH secretion by cultured nonenzymatically dispersed pituitary tumour cells from three patients with Nelson's syndrome. Cyproheptadine (1-10 mumol/l) and desmethylcyproheptadine (1-10 mumol/l) suppressed ACTH secretion significantly (P less than 0.01), while serotonin (10 mumol/l) did not have a direct effect. Serotonin was also not able to reverse the (desmethyl)cyproheptadine-mediated inhibition of ACTH release. Sodium valproate and GABA did not exert a direct effect on hormone release by these cultured pituitary tumour cells. It is suggested that cyproheptadine-mediated inhibition of ACTH release in Nelson's syndrome might be effected by a direct non-serotonin-related effect on the pituitary tumour, while sodium valproate suppresses ACTH release by a suprahypophysial action.

Adrenocorticotropic Hormone↗
PubMed1982

Effect of tamoxifen administration on prolactin release by invasive prolactin-secreting pituitary adenomas.

Bromocriptine treatment of patients with invasive prolactin (PRL)-secreting pituitary adenomas does not invariably result in normalization of the plasma PRL levels. We previously showed that the antiestrogenic drug tamoxifen inhibited hormone release from transplantable PRL-secreting pituitary tumors in rats. In 8 patients with invasive PRL-secreting pituitary adenomas with extrasellar extension, the effect of the administration of tamoxifen was investigated on the plasma PRL concentration and on the bromocriptine-mediated inhibition of PRL release. Treatment for 5 days with tamoxifen (20 mg/day) suppressed plasma PRL levels as measured in 5 samples over the day significantly by 20 +/- 3% (means +/- SEM; p less than 0.01). During tamoxifen administration the inhibition of PRL secretion by 2.5 mg bromocriptine was further suppressed by 36 +/- 7%, in comparison with the plasma PRL levels after bromocriptine alone (p less than 0.01). Tamoxifen administration suppressed PRL release in patients with giant invasive PRL-secreting pituitary adenomas, and it had a slight but significant additive or potentiating effect on the bromocriptine-mediated inhibition of PRL secretion. However, despite the simultaneous administration of bromocriptine and tamoxifen, normalization of the circulating PRL levels was not reached in this type of patient.

Adenoma↗
PubMed1982

Testosterone secretion by cultured arrhenoblastoma cells: suppression by a luteinizing hormone-releasing hormone agonist.

A patient with virilization was studied. The basal urinary excretion of 17-ketosteroids was at the upper limit of normal, but the plasma testosterone concentration was greatly elevated. Testosterone secretion could be stimulated by hCG, suppressed by dexamethasone, and was not affected by ACTH. At operation, an arrhenoblastoma of the left ovary was found. Isolated tumor cells in culture secreted testosterone. The addition of a LRH agonist (10 ng/ml) suppressed the secretion of testosterone by 50% (P less than 0.01). The inhibiting effect of a LRH agonist on steroidogenesis suggests that LRH receptors were present on this tumor and that treatment with LRH agonists might be beneficial in patients with metastatic steroid hormone-secreting ovarian and testicular tumors.

17-Ketosteroids↗