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Biomedical subjects

O Serri

Publications and source records attributed to O Serri.

At least 37 records · Page 2Linked to original sources
PubMed1992

Octreotide inhibits insulin-like growth factor-I hepatic gene expression in the hypophysectomized rat: evidence for a direct and indirect mechanism of action.

Somatostatin and somatostatin analogs are known to interact with the GH-insulin-like growth factor (IGF)-I axis by inhibiting GH secretion and consequently hepatic IGF-I production. Indirect evidence suggests that octreotide, a somatostatin analog, reduces serum IGF-I levels relatively more than expected from GH reduction, implying a GH-independent pathway of action. To study the role of octreotide in the regulation of IGF-I production, independently of endogenous GH, we used the hypophysectomized (hypox) rat to measure hepatic IGF-I expression and also employed cultured rat hepatocytes to examine whether octreotide has any direct effect on the production of IGF-I. Forty male hypox Sprague-Dawley rats were randomized into 4 groups to receive daily injections for 3 days of either saline, human GH (hGH) (100 g), octreotide (100 g twice), or both hGH (100 g) and octreotide (100 g twice). GH stimulated serum IGF-I levels to 104 +/- 10 micrograms/liter as compared to saline (26 +/- 2 micrograms/liter). Octreotide alone had no effect, but combining octreotide and hGH significantly reduced the hGH-induced rise in the IGF-I levels (52 +/- 6 micrograms/liter). The relative expression of hepatic IGF-I in the rats treated with hGH increased by 4-fold compared to that in the saline-treated rats. Octreotide administered simultaneously with hGH potently blocked the hGH-induced IGF-I expression to control levels. In cultured hepatocytes, IGF-I mRNA levels maximally stimulated by combining bGH and glucagon were significantly inhibited in the presence of octreotide at low concentrations (0.3 and 3 ng/ml) by 25% and 45%, respectively. In contrast, high concentrations of octreotide (30 and 300 ng/ml) had no significant effect on IGF-I mRNA abundance. We conclude that: 1) octreotide inhibits IGF-I serum levels and hepatic gene expression in the hypox rat; and 2) octreotide can inhibit partially the direct effects of GH and glucagon on hepatic IGF-I production.

Animals↗
PubMed1991

The clinical and endocrine outcome to trans-sphenoidal microsurgery of nonsecreting pituitary adenomas.

From 1962 to 1987, 126 patients underwent trans-sphenoidal surgery for primary treatment of pituitary adenomas unassociated with clinical or biochemical evidence of hormonal overproduction. There were 73 male and 53 female patients (mean age, 50 +/- 12 years). Before surgery, 56% of the patients (70 of 124) had headaches, 74% (94 of 126) had deterioration of vision, and 12% (15 of 126) had ophthalmoplegia. Endocrine evaluation revealed the presence of hypogonadism in 75% (87 of 115), adrenal insufficiency in 36% (46 of 126), and hypothyroidism in 18% (21 of 122). Plasma prolactin was increased in 65% (56 of 86) with a mean level of 39 +/- 14 micrograms/l (normal, 3 to 20 micrograms/l). Radiologic enlargement of the sella turcica was documented in all cases: 67% (84 of 126) had enclosed and 33% (42 of 126) had invasive adenomas. After surgery, vision was normalized or improved in 75% (71 of 94) of the patients. Thyroid, adrenal, and gonadal functions were improved in 14% (three of 22), 41% (19 of 46), 11% (ten of 87), were unchanged in 82% (100 of 122), 77% (97 of 126), 89% (102 of 115), and worsened in 15% (19 of 22), 8% (ten of 126), 3% (102 of 115), respectively. Permanent diabetes insipidus occurred in 5% (seven of 126). Two patients died during the immediate postoperative period. The recurrence rate in patients with a mean follow-up of 6.4 +/- 4.2 years was 21% (15 of 71). These data indicate that trans-sphenoidal microsurgery is an effective and safe initial treatment for patients with nonsecreting pituitary adenoma and may reverse hypopituitarism.

Adenoma↗
PubMed1991

Somatostatin analogue, octreotide, reduces increased glomerular filtration rate and kidney size in insulin-dependent diabetes.

To determine whether treatment with a somatostatin analogue can reduce kidney hyperfiltration and hypertrophy in insulin-dependent diabetes mellitus, we studied 11 patients with insulin-dependent diabetes mellitus and glomerular hyperfiltration. The patients were assigned randomly to receive continuous subcutaneous infusion of either octreotide, 300 micrograms/24 h (five patients) or placebo (six patients) for 12 weeks. At baseline, mean glomerular filtration rate and mean total kidney volume were not significantly different in the two groups. However, after 12 weeks of treatment, the mean glomerular filtration rate was significantly lower in the octreotide group (136 mL/min per 1.73 m2; range, 91 to 158 mL/min per 1.73 m2) than in the placebo group (157 mL/min per 1.73 m2; range, 138 to 184 mL/min per 1.73 m2). Furthermore, the mean total kidney volume was significantly lower after treatment in the octreotide group (379 mL/1.73 m2; range, 307 to 454 mL/1.73 m2) than in the placebo group (389 mL/1.73 m2; range, 347 to 465 mL/1.73 m2). Glycemic control did not change significantly in either group. We conclude that subcutaneous infusion of octreotide for 12 weeks reduces increased glomerular filtration rate and kidney size in patients with insulin-dependent diabetes mellitus despite the fact that glycemic control remains unchanged.

Adult↗
PubMed1991

Effects of acute and prolonged glucose excess on growth hormone release by cultured rat anterior pituitary cells.

The aim of this study was to verify whether prolonged exposure of cultured rat anterior pituitary cells to high glucose can alter growth hormone (GH) release and responsiveness to secretagogues. Therefore, we cultured anterior pituitary cells obtained from normal male Sprague-Dawley rats in presence of normal (6 mM) or high (22 mM) glucose concentrations. After 3 days, the acute effects of glucose, growth hormone-releasing factor (GRF), dibutyryl cyclic AMP(db-cAMP) and somatostatin were studied during 2-hour incubations. High glucose did not alter basal GH release from cells cultured in 6 mM glucose. However, basal GH release from cells cultured in 22 mM glucose was moderately higher in the 2-hour incubation (by 46%) than in cells cultured in 6 mM glucose. In contrast, GH stimulation by GRF or db-cAMP was significantly reduced in cells cultured in 22 mM as compared to cells cultured in 6 mM glucose. This inhibitory effect of high glucose on GRF-stimulated GH release was completely reversible after 24 h of exposure of the cultured cells to 6 mM glucose and testing on the 4th day of culture. Finally, GH inhibition by somatostatin was also attenuated in cells cultured with high glucose. We conclude that prolonged exposure to high glucose could act directly at the pituitary level to modulate GH release and responsiveness.

Animals↗
PubMed1990

Long term treatment with CV 205-502 in patients with prolactin-secreting pituitary macroadenomas.

CV 205-502, a new long-acting nonergot dopamine agonist, was given to 15 patients (6 women and 9 men) with PRL-secreting pituitary macroadenomas. The compound was administered in a single daily dose for a period of 6-12 months. The treatment resulted in normalization of plasma PRL levels (less than or equal to 20 micrograms/L) in 5 of 6 women at a mean dose of 135 micrograms (range, 75-300 micrograms) and in 6 of 9 men at a mean dose of 192 micrograms (range, 75-300 micrograms). Among patients for whom computed tomographic scans were available before and after at least 6 months of therapy, definite tumor shrinkage occurred in 6 of 7 patients. Libido was improved in 5 of 6 women and in 6 of 8 men, galactorrhea disappeared in all cases (3 women and 1 man) and menses resumed in 3 of 5 women. Plasma testosterone rose to normal levels in 3 of 6 men who were not receiving testosterone injections. The PRL response to TRH was blunted in 4 of 6 patients with normalized basal PRL. Serum total cholesterol was reduced by CV 205-502 treatment in women from 5.35 +/- 0.49 to 4.63 +/- 0.51 mmol/L (P = 0.031) and in men from 5.93 +/- 0.89 to 5.28 +/- 0.82 mmol/L (P = 0.045). Side-effects included mainly headache, nausea, and dizziness. One side-effect or more occurred transiently and with mild intensity in 14 patients. No patient discontinued the therapy because of side-effects. In conclusion, CV 205-502 appears to be a safe and valuable compound in the treatment of patients with PRL-secreting macroadenomas.

Adult↗
PubMed1989

Effect of dietary restriction and repeated growth hormone-releasing factor injections on growth hormone response to growth hormone-releasing factor in obese subjects.

The response of serum growth hormone (GH) to a test bolus of growth hormone-releasing factor (GRF) (1 micrograms/kg, IV) was examined in eight obese subjects (166% +/- 8% ideal body weight [IBW] during a weight-maintaining control period and after 2 weeks of hypocaloric feeding (750 kcal). During the period of hypocaloric feeding subjects received either repetitive GRF 1 micrograms/kg, IV (GRF group, n = 6) at 9 AM, 1 PM, and 5 PM three times a week, or saline injections (placebo group, n = 6) at the same intervals. Four subjects were studied twice, several months apart, each receiving GRF and placebo treatments. Nitrogen balance was determined daily throughout the study. We also examined GH response to the GRF test in seven normal-weight subjects (106% +/- 6% IBW]. During the control period, obese subjects demonstrated a blunted GH response to GRF expressed as peak height or GH area under the curve (0 to 120 minutes) compared with normal subjects (P less than .005). At the end of the hypocaloric feeding, mean GH peak height after the GRF test was unchanged in the placebo group compared with the control period. GH release was significantly increased only during the second hour of testing (P less than .025). However, the GRF group demonstrated an increase in both mean GH peak height (P less than .025) and GH release during the first and second hours of testing (P less than .025) compared with the control period. Weight loss and blood glucose, triglycerides, FFA, amino acids, insulin, and T3 changes were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Growth hormone rebound after cessation of sms 201-995 treatment in acromegaly.

We studied a 42-year-old woman who had persistent active acromegaly despite conventional therapies. She was treated for 6 months with SMS 201-995. Her mean plasma growth hormone GH values decreased during treatment from 9.1 +/- 1.2 to 6.6 +/- 1.2 micrograms/L. One month after the withdrawal of SMS 201-995, the plasma GH level increased to 24.4 micrograms/L (P less than 0.001). This elevation was clinically silent and transitory, as GH levels decreased 8 months later to 6.9 +/- 1.3 micrograms/L. Furthermore, at the beginning of therapy, her intractable headache was completely relieved; however, it progressively resumed under therapy. In conclusion, cessation of SMS 201-995 may be followed in some acromegalic patients by a rebound of plasma GH levels. This rebound suggests that SMS 201-995 decreases GH levels by an inhibition of its release from the pituitary. Furthermore, SMS 201-995 may relieve intractable headache in some acromegalic patients, but tolerance to the analgesic effect may develop.

Acromegaly↗
PubMed1989

Growth hormone-releasing factor increases serum prolactin concentrations in normal subjects and in patients with pituitary adenomas.

We have examined the serum growth hormone (GH) and prolactin (PRL) response to growth hormone releasing factor (hGRF-(1-44)NH2 (GRF) 1 microgram/kg i.v. bolus) in 16 acromegalic patients (eight of whom were hyperprolactinaemic), 13 patients with microprolactinoma, and 14 healthy subjects. The GH responses to TRH and to the somatostatin analogue SMS 201-995 were also studied in acromegalic patients. In these, and in patients with microprolactinoma, GH responses after GRF (P less than 0.001 vs saline) were variable. The absolute GH increase (calculated as area under the curve) in acromegalic patients (2489 +/- 920 micrograms/l min), or in patients with microprolactinoma (1322 +/- 279 micrograms/l min) was not different from that in controls (2238 +/- 633 micrograms/l min). In addition, a significant increase in PRL release was observed after GRF in comparison to saline in acromegalic patients (P less than 0.01), in patients with microprolactinoma and in normal subjects (P less than 0.001). The PRL increase was significantly correlated with basal PRL levels in acromegalic patients (r = 0.99, P less than 0.001) and in patients with microprolactinomas (r = 0.61, P less than 0.05). Furthermore, a significant correlation was found between GH rise after GRF and basal GH, and between GH rise after GRF and GH decrement after SMS in patients with acromegaly. These results suggest that GRF can stimulate PRL release by actions on the normal pituitary and on pituitary adenomas, including microprolactinomas. Moreover, the data suggest that in acromegaly there is a relative functional deficiency of hypothalamic somatostatin.

Acromegaly↗
PubMed1989

Temporal changes in prolactin and corticosterone response during chronic treatment with d-fenfluramine.

In order to elucidate the mechanism of development of tolerance to the anorectic effect during chronic treatment with d-fenfluramine (d-F), we examined the temporal changes induced by d-F in food intake and prolactin (PRL) and corticosterone secretion. Male Sprague-Dawley rats were treated for 14 days with d-F (2.5 mg/kg i.p.) or saline twice daily and were given free access to food and water. Groups of 8 rats were sacrificed 30 min after d-F or saline injection at days 1, 4 and 14 for measurements of serum PRL and corticosterone. Food intake and weight gain were reduced significantly by d-F during the first 2-3 days of treatment but not thereafter. Compared with saline, d-F initially increased PRL (57 +/- 9 vs. 7 +/- 0.7 ng/ml) and corticosterone (42 +/- 2 vs. 14 +/- 3 micrograms/dl) serum concentrations. At 4 days, PRL was still significantly increased (43 +/- 5 vs. 10 +/- 4 ng/ml) but corticosterone returned to basal levels. At 14 days, PRL and corticosterone concentrations in the d-F group were not different from corresponding values in the saline group. To verify whether the loss of corticosterone and PRL responses to d-F was not due to a depletion of hormone stores, direct stimulation of corticosterone with corticotrophin and of PRL with metoclopramide were made at days 4 and 14, respectively. Corticotrophin (0.25 mg/kg i.p.) increased corticosterone concentrations similarly in d-F-treated (45 +/- 8 micrograms/dl) and in saline-treated rats (51 +/- 7 micrograms/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Mixed growth hormone and prolactin-secreting human pituitary adenomas: a pathologic, immunocytochemical, ultrastructural, and immunoelectron microscopic study.

A study of 30 adenomas from patients with signs of growth hormone (GH) and prolactin (PRL) hypersecretion revealed the presence of mammosomatotroph cells (MSC) containing both hormones in all cases. Although the number of immunostained cells varied from case to case, in 14 of 25 tumors, all stained cells were MSC. Nine tumors had the ultrastructural appearance of densely granulated growth hormone adenomas, while 11 cases resembled sparsely granulated growth hormone adenomas with frequent fibrous bodies. Exocytosis was present in six of these 11 cases, a feature unusual for pure growth hormone adenomas. Nine tumors consisted of a mixture of cells with the morphology of GH and PRL cells. In the four cases examined, immunoelectron microscopy using double immunolabeling with protein A-gold particles revealed the presence of secretory granules containing both hormones in some tumor cells recognized as mammosomatotroph cells.

Adenoma↗
PubMed1988

Defective dopaminergic regulation of prolactin secretion in patients with hyperprolactinemia.

In order to evaluate the dopaminergic control of the lactotroph, we examined the plasma prolactin response to metoclopramide (a dopamine receptor blocker, 10 mg iv bolus) and to dopamine (1 microgram/Kg/min iv infusion for 120 min) in 52 hyperprolactinemic female patients and 19 healthy volunteer women. Three diagnostic categories were included: "idiopathic" hyperprolactinemia (21), microadenoma (24), and macroadenoma (7). Patients from all groups showed a marked blunting of the prolactin response to metoclopramide as compared to the prolactin rise in normal women (p less than 0.001). However, normal responses were observed in 8 patients with idiopathic hyperprolactinemia and in one patient with adenoma. The magnitude of the prolactin response to metoclopramide (percent of baseline level) correlated negatively with the level of basal prolactin in each group except for macroadenoma patients. Dopamine infusion significantly (p = 0.015) reduced the mean plasma prolactin levels in hyperprolactinemic patients and normal women. However, patients with idiopathic hyperprolactinemia were hyposensitive to dopamine (p less than 0.05). Furthermore, microadenoma patients were less responsive to dopamine suppression than were the patients with macroadenoma (p less than 0.05). The results indicate the presence of a relative resistance to dopamine in patients with idiopathic hyperprolactinemia and in patients with microadenoma. They also suggest that in these patients, the decrease in prolactin response to metoclopramide may be explained by the relative refractoriness to endogenous dopamine.

Adenoma↗
PubMed1987

Hyperprolactinemia associated with clinically silent adenomas: endocrinologic and pathologic studies; a report of two cases.

Pituitary adenomas containing adrenocorticotropic hormone (ACTH) in one case, and ACTH, beta-lipotropin, and beta-endorphin in the other, were demonstrated in two patients who had amenorrhea-galactorrhea and hyperprolactinemia with no manifestation of Cushing's disease. Neither adenoma contained prolactin (PRL). Initial bromocriptine therapy resulted in cessation of amenorrhea-galactorrhea and normalization of PRL levels. However, there was radiologic evidence of tumor enlargement in both patients. After pituitary adenomectomy, the two patients resumed regular menses and normal PRL dynamics. These patients illustrate the need for bromocriptine therapy for possible enlargement of their pituitary adenomas. The diagnosis of silent corticotroph adenoma should be kept in mind.

Adenoma↗
PubMed1987

Distinctive features of prolactin secretion in acromegalic patients with hyperprolactinaemia.

We have investigated the relationship between the plasma PRL concentrations of 98 untreated acromegalic patients and the GH levels during basal and dynamic conditions. Hyperprolactinaemia was present in 27 patients. In patients with marked hyperprolactinaemia (PRL greater than 80 ng/ml or greater than 1600 mU/l), basal plasma PRL and the TRH-induced response correlated with basal plasma GH (correlation coefficients of 0.9, P less than 0.001 and 0.74, P less than 0.02, respectively). The PRL response to TRH also correlated with GH response to TRH (r = 0.38, P less than 0.01). In contrast, in patients with moderately elevated PRL (20 to 80 ng/ml), and in those with normal plasma PRL (less than 20 ng/ml or less than 400 mU/l), no such correlations were found. Immunostaining for PRL was positive in 24 out of 25 adenomas of patients with hyperprolactinaemia, while no PRL was found in the tumour tissue of 10 normoprolactinaemic patients. In conclusion, our data suggest the existence of two populations of acromegalic patients with hyperprolactinaemia, one group with correlations between GH and PRL secretion, and the other without.

Acromegaly↗
PubMed1987

Growth hormone releasing factor stimulates and somatostatin inhibits prolactin release from human mixed somatotroph-lactotroph adenomas in perifusion.

The effects of human growth hormone-releasing factor (hGRF) and somatostatin on growth hormone (GH) and prolactin (PRL) secretion in perifusion of dispersed cells of human GH-secreting adenomas, obtained from seven acromegalic patients with hyperprolactinaemia, were examined. Six adenomas stained for both GH and PRL on immunohistochemical examination, and one contained only GH. GH release was consistently stimulated in a dose-dependent manner by hGRF (0.01, 0.1 and 1.0 nM) in all seven adenomas studied. PRL release was undetectable in two adenomas. In the other five, hGRF stimulated PRL release and the response was dose related. Furthermore, the PRL response was significantly correlated with the GH response to hGRF. When cells were perfused with somatostatin (1 nM), GH and PRL secretion induced by hGRF was completely antagonized. We also evaluated the effect of hGRF pretreatment on the subsequent GH response to hGRF in two adenomas. hGRF pretreatment (1 nM) for 210 min reduced the GH response to a subsequent hGRF challenge (100 nM) in one tumour but not in the other. In conclusion, the PRL response is similar to the GH response in mixed GH and PRL-secreting adenomas after exposure to GH release-stimulating and inhibiting hormones. After prolonged exposure to hGRF, some adenomas remain responsive to further stimulation with hGRF, whereas others do not.

Adenoma↗
PubMed1987

The effect of d-fenfluramine on anterior pituitary hormone release in the rat: in vivo and in vitro studies.

Administration of d-fenfluramine, a serotonin-releasing drug, to male rats induced a dose-dependent increase in both serum prolactin and corticosterone concentrations. Serum growth hormone levels increased, but not significantly, at a dose of 1.25 mg/kg i.p. and decreased significantly at higher doses. When rats were pretreated with the serotonin uptake inhibitor fluoxetine (10 mg/kg i.p.) 30 min prior to injection of d-fenfluramine (5 mg/kg i.p.), the serum prolactin response to d-fenfluramine was partially inhibited, whereas the growth hormone response was not significantly modified. Fluoxetine pretreatment increased the serum corticosterone to the same level as did d-fenfluramine. d-Fenfluramine's effect on prolactin and growth hormone release was further tested in a hypothalamic-pituitary in vitro system. The addition of d-fenfluramine (5-500 ng/mL) for 30 min to rat hypothalami resulted in an enhancement of prolactin and growth hormone-releasing activities. These were expressed as the ability of the media in which the hypothalami had been incubated to stimulate prolactin and growth hormone release by cultured pituitary cells. The data suggest that the effect of d-fenfluramine on prolactin secretion is exerted through the hypothalamus and is probably mediated, at least partially, by a serotoninergic mechanism. The mechanism of d-fenfluramine's effect on corticosterone and growth hormone release needs further evaluation.

Animals↗
PubMed1987

Dual action of dopamine on growth hormone release in vitro.

The effect of dopamine (DA) on growth hormone (GH) release was studied in perifused freshly dispersed rat anterior pituitary cells. Pulses of DA (0.01-100 nmol/l), each applied for 30 min, resulted in a prompt rise in GH release. This effect was reversible, concentration-dependent and partially antagonized by metoclopramide, a DA antagonist. The effect of DA was further tested on GH-stimulated secretion by human GH-releasing factor (hGRF). Perifusion with hGRF (6.25 pmol/l) for 2 min elicited an immediate rapid increase in GH release which lasted 20 min. Pretreatment of cells with DA (100 nmol/l) for 10 min and a subsequent hGRF challenge during continuation of DA perifusion significantly reduced the effect of hGRF pulses on GH release. The present data suggest that DA has direct opposite actions at the somatotroph level, stimulating the basal GH release and inhibiting the hGRF-induced GH secretion, and may thus be an important modulator of GH release.

Animals↗
PubMed1987

Growth hormone responsiveness in vivo and in vitro to growth hormone releasing factor in the spontaneously diabetic BB Wistar rat.

In order to determine whether there is an abnormality in the pituitary responsiveness to GRF in the diabetic rat, we examined the in vivo and in vitro effects of hGRF-44 NH2 (hGRF) on growth hormone (GH) release in the spontaneously diabetic BB Wistar rat. Under pentobarbital anesthesia, hGRF was injected intravenously at a dose of 500 ng/kg in male diabetic BB Wistar rats (n = 11) and in male control Wistar rats matched for weight (n = 11). Basal serum GH concentrations were significantly lower in the diabetic group, (123 +/- 5 ng/ml, mean +/- SEM) than in the control group (362 +/- 15 ng/ml). However, the GH response to hGRF was significantly greater in the diabetic group (GH increment 873 +/- 153 ng/ml) than in the control group (268 +/- 91 ng/ml). The effect of hGRF was further tested in a perifusion system of freshly dispersed anterior pituitary cells of diabetic BB Wistar rats and control Wistar rats. Basal secretion rate of GH from cells of diabetic rats (0.85 +/- 0.06 microgram/2 pituitaries X 2 min) was lower than that from cells of control rats (1.60 +/- 0.18 micrograms/2 pituitaries X 2 min). The GH response to 2-min pulses of hGRF at concentrations of 1.56, 6.25, and 25 pM with and without somatostatin 10(-9) M was significantly greater in the diabetic group than in the control group. In conclusion, there is in the spontaneously diabetic rat an increased in vivo and in vitro GH responsiveness to exogenous hGRF suggesting an abnormality of GH regulation at the pituitary level.

Animals↗