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PubMed1992

Endocrine effects of new bombesin/gastrin-releasing peptide antagonists in rats.

Four new and specific pseudononapeptide bombesin/gastrin-releasing peptide (GRP) receptor antagonists, containing the D-forms of Trp or Trp analogue (Tpi) at position 6, were studied for their effects on the endocrine pancreas and GRP-(14-27)-induced gastrin release in pentobarbital-anesthetized rats. One of the analogues, D-Tpi6,Leu13-psi (CH2NH)Leu14-bombesin-(6-14) (RC-3095), was injected into the lateral brain ventricle just preceding intracerebroventricular administration of GRP-(14-27) to evaluate its antagonistic effect on GRP-induced serum growth hormone (GH) suppression. Analogues RC-3095, D-Trp6,Leu13-psi (CH2NH)Leu14-bombesin-(6-14) (RC-3125), and D-Trp6,Leu13-psi (CH2NH)Phe14-bombesin-(6-14) (RC-3420), but not D-Tpi6,Leu13-psi (CH2NH)Phe14-bombesin-(6-14) (RC-3105), significantly (P < 0.01) inhibited GRP-(14-27)-stimulated serum gastrin secretion. Analogues RC-3095, RC-3420, and RC-3105, but not RC-3125, demonstrated significant (P < 0.05) antagonistic activities on GRP-(14-27)-stimulated plasma glucagon secretion. Intracerebroventricular injection of RC-3095 (10 micrograms) immediately before GRP-(14-27) (1 microgram) completely prevented the GRP-(14-27)-induced serum GH suppression. These results indicate that 1) marked differences exist in the ability of these analogues to antagonize GRP-(14-27)-induced gastrin or glucagon release, suggesting the existence of different bombesin/GRP receptor subtypes, and 2) the central effect of bombesin/GRP on GH release from the pituitary is probably mediated through specific bombesin/GRP receptors.

Amino Acid Sequence↗

PubMed1985

Endocrine effects of low dose aminoglutethimide as an aromatase inhibitor in the treatment of breast cancer.

The endocrine effects of low dose (62.5 mg, twice a day) aminoglutethimide (AG), without hydrocortisone (HC), escalating at monthly intervals to a conventional dose of AG (500 mg twice a day) combined with HC, were studied in 33 postmenopausal breast cancer patients. Pretreatment serum concentrations of oestrone (E1) and oestradiol (E2) were significantly suppressed by 62.5 mg of AG twice a day. Although further suppression of E1 appeared to occur with 125 mg of AG twice a day, this was not statistically significant. For E1 and E2, higher doses of AG or combined AG and HC failed to cause further significant suppression compared with that obtained at 125 mg of AG twice a day. Significant rises in serum androstenedione were found with all doses of AG alone, although pretreatment concentrations of androstenedione were not significantly altered by combined AG and HC treatment. Mean pretreatment concentrations of dehydroepiandrosterone sulphate (DHA-S) were significantly suppressed by 62.5 mg of AG twice a day and further marked suppression occurred on combined AG and HC therapy. Serum cortisol, aldosterone and plasma ACTH concentrations showed no significant alterations throughout treatment. Aminoglutethimide is as effective at 125 mg twice a day without HC in its suppression of oestrogen levels as at 500 mg twice a day with HC, and its use in this form warrants clinical evaluation.

Adrenocorticotropic Hormone↗

PubMed1983

Endocrine effects of the H2-receptor antagonists cimetidine and ranitidine.

This paper reviews investigations on the endocrine effects of two H2-receptor antagonists, cimetidine and ranitidine. Cimetidine has hyperprolactinaemic properties and interferes with the peripheral activity of the sexual hormone (DHT) and probably with the pituitary LH secretion. A possible effect on TSH and thyroid hormone secretion or peripheral metabolism is suggested. Ranitidine seems to have no central or peripheral effects (after both acute and chronic administration) on sexual hormones. High doses (300 mg i.v. bolus) of the drug induce a significant increase in prolactin basal levels, whereas no effects follow oral administration. The effects on PRL are sex-related and less marked than those obtained with cimetidine. The chronic administration of this drug does not affect basal or TRH-stimulated PRL levels. No effects were apparent on TSH serum levels after either oral or i.v. acute administration, whereas lower basal and TRH-stimulated T4 values were registered after chronic treatment. On the basis of these results, a possible interference of ranitidine on iodothyronine metabolism can be suggested.

Animals↗

PubMed1989

[Comparison of endocrine effects of hypotension induced by sodium nitroprusside, trimetaphan camsylate and a nitroprusside-trimetaphan mixture in rabbits].

Endocrine effects of hypotension induced by nitroprusside, trimetaphan and a nitroprusside-trimetaphan mixture were studied in 34 male rabbits under halothane anesthesia. They were randomly divided into four groups; nitroprusside (group N; n = 8), trimetaphan (group T; n = 10), a nitroprusside-trimetaphan mixture (group M; n = 8) and controls (group C; n = 8). No change was noted in plasma catecholamines measured in group C throughout the experiment, but plasma renin activity decreased progressively. During induced hypotension, plasma catecholamines and plasma renin activity of group N were significantly higher than the control value. In contrast, in group T plasma epinephrine decreased significantly. On the other hand, in group M, plasma renin activity showed a slight but not significant increase, while plasma catecholamines remained unchanged. This may have occurred since a mixture of nitroprusside and trimetaphan produced the dissociation of renin-angiotensin-sympathoadrenal loop. In conclusion, these results suggest that a nitroprusside-trimetaphan mixture is a useful method for hypotensive anesthesia by inhibiting the excessive activation of renin-angiotensin-sympathetic system.

Animals↗

PubMed1987

Sequential combination of tamoxifen and high dose medroxyprogesterone acetate: therapeutic and endocrine effects in postmenopausal advanced breast cancer patients.

A sequential combination of tamoxifen and medroxyprogesterone acetate has been evaluated in 42 postmenopausal untreated patients with metastatic breast cancer. Patients received tamoxifen 10 mg b.i.d., days 1-14, followed by medroxyprogesterone acetate 500 mg b.i.d., days 15-28, orally in an alternating sequence until progression. Twenty-two out of 40 evaluable patients showed an objective response to treatment (55%, 95% confidence limits 38-75%). A significantly higher response rate was observed in patients with age greater than or equal to 70 years, with soft tissue dominant lesions and with only one metastatic site. Median time to progression was 41 weeks and the median survival time 88 weeks. In 4 cases treatment was discontinued because of severe toxicity while in the remaining patients no toxicity (20 patients) or mild side effects (17 patients) have been observed. After 2 months of therapy, this combination showed a progestogenic effect on the endocrine parameters inducing a significant decrease of SHBG, gonadotropins, testosterone and cortisol. These preliminary clinical results and the moderate toxicity of the sequential combination support the need to further investigate this approach.

Adult↗

PubMed1988

Endocrine effects of 17 alpha-hydroxyprogesterone caproate during early pregnancy: a double-blind clinical trial.

The clinical and endocrine effects of progestogen therapy in early pregnancy were investigated using a double-blind randomized trial in 64 patients who had a viable fetus at 6 weeks gestation and had an increased risk of miscarriage. The patients were randomly allocated to receive either 17 alpha-hydroxyprogesterone caproate or a placebo between 7 and 12 weeks gestation. Four fetal ultrasonographic variables and 17 maternal endocrine variables were studied in each woman. Only four maternal serum variables (17 alpha-hydroxyprogesterone, prolactin, thyroxin and thyroxin binding globulin) rose significantly. The serum progesterone levels in the hormone supplemented group were on average 20% higher than in the placebo group but the difference was not statistically significant. However, the relation between the progesterone levels and the fetal outcome was not clear. Therefore it is not advisable to prescribe 17-OHP-C during early pregnancy to prevent a miscarriage.

17 alpha-Hydroxyprogesterone Caproate↗

PubMed2002

Endocrine effects of centrally injected nociceptin in the rat.

In the present study we investigated the mechanisms involved in the endocrine effect of nociceptin/orphanin FQ (OFQ) in the rat and the possible interaction between OFQ and morphine in the control of growth hormone (GH) secretion. The intracerebroventricular administration of OFQ (2.3 or 23 microg/rat, i.c.v.) in freely moving male rats caused an increase in the secretion of both GH and prolactin (PRL). The possible involvement of the catecholaminergic (CA) system was studied by administering OFQ to CA-depleted rats (rats given 200 mg/kg of alpha-methyl-p-tyrosine subcutaneously 2 h before the i.c.v. dose of OFQ). In these CA-depleted rats, administration of OFQ (23 microg/rat, i.c.v.) did not stimulate GH secretion, whereas it significantly enhanced PRL secretion. In rats anesthetized with ketamine, which induces a significant increase of GH, PRL and corticosterone secretion by activating the sympathetic tone, OFQ (23 microg/rat, i.c.v.) did not modify GH and corticosterone levels, whereas again it significantly potentiated PRL secretion. Overall these results indicate that CA system is involved in the stimulatory action of OFQ on GH but not on PRL secretion. In fact the stimulation of PRL, but not that of GH, was still evident after impairment of the CA system. Pretreatment with OFQ (23 microg/rat, i.c.v.) attenuated the GH secretion induced by morphine (1 mg/kg, given by intra-arterial injection), thus showing a negative interaction between OFQ and morphine in the control of GH secretion.

Analgesics, Opioid↗

PubMedDate not supplied

[Pressor, renal and endocrine effects of systemic infusion of L-arginine in hypertensive patients].

In this study we compared the pressor, renal and endocrine effects of the physiological precursor of endothelial derived nitric oxide, L-arginine, with D-glucose, a substrate inactive on nitric oxide. Ten subjects with mild to moderate primary hypertension underwent infusion with either L-arginine (5 patients) or D-glucose (5 patients). The substances were infused over 25 min at equiosmolar rates, preceded and followed by a 25-min saline infusion. Blood pressure (BP) and heart rate were monitored at 3-min intervals; hormonal and humoral variables, inulin and para-aminohippurate clearance, and electrolyte excretion were measured at the end of each period at maximum diuresis. L-arginine and D-glucose brought about comparable increases in serum osmolality and similar hemodilution as compared with control saline. During L-arginine infusion, systolic and diastolic BP dropped by 16.6% and 11% respectively and recovered during the post-infusion period. Heart rate, plasma renin activity, and plasma norepinephrine did not change significantly. The percent BP decrease induced by L-arginine was significantly greater than that caused by D-glucose. Glomerular filtration rate remained stable, and renal plasma flow increased with both substances. However, only L-arginine stimulated markedly natriuresis, kaliuresis, and chloruresis. It also seemed to induce systemic acidosis, possibly as a consequence of hydrochloric acid generated during its metabolism. Circulating insulin, atrial natriuretic peptide, growth hormone, and glucagon levels increased, and plasma aldosterone remained unchanged during L-arginine infusion. During D-glucose infusion, insulin was stimulated and the other hormones were inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

PubMed2005

Endocrine effects of relaxin overexpression in mice.

Relaxin is a small peptide hormone with a variety of biological functions. To investigate the systemic endocrine effects of relaxin, we produced mice with transgenic overexpression of the Rln1 gene, Tg(Rln1), driven by rat insulin 2 promoter. The expression of relaxin was detected in the pancreas of the transgenic animals. An analysis of the sera from the transgenic animals revealed at least 20-fold elevation of the level of bioactive relaxin. Transgenic animals had normal viability and fertility in both sexes. Transgenic overexpression of Rln1 did not rescue the undescended testis phenotype in Insl3-deficient males, suggesting that in vivo relaxin does not interact with the insulin-like 3 factor receptor, leucine-rich repeats-containing G protein-coupled receptor 8, Lgr8. Phenotypically, the excess of relaxin resulted in hypertrophic nipple development in virgin female mice. Deletion of the relaxin receptor, leucine-rich repeats-containing G protein-coupled receptor 7, Lgr7, in Tg(Rln1) animals abrogated the development of enlarged nipples in females, indicating that relaxin exerts its effect through Lgr7 alone. The levels of previously defined targets of relaxin signaling, such as matrix metalloproteinases 2 and 9, vascular endothelial growth factor, or nitric oxide, were similar in the sera of the transgenic and wild-type mice. However, the total plasma protein concentration in male Tg(Rln1) mice was lower than that in control animals. The livers of male Tg(Rln1) mice exhibited significantly higher hydroxyproline content, indicative of increased collagen deposition. Our results indicate that relaxin overexpression causes gender-specific changes in liver collagen metabolism.

Animals↗

PubMed1994

Endocrine effects of Lycopus europaeus L. following oral application.

Lycopus extracts are used in folk medicine for the treatment of hyperthyroid symptoms. Diverse effects on the pituitary thyroidal system as well as on the pituitary gonadal system could be confirmed in experimental studies. But till now endocrine effects of Lycopus extracts in experimental animals were observed after parenteral application only. Therefore in this investigation an ethanolic extract of Lycopus europaeus was applied orally to rats, diverse endocrine parameters were measured between 3 and 24 h later and the effects compared to an i.p. treated group. The plant extract given p.o. caused a long lasting (for a period of more than 24 h) decrease of T3 levels, presumably as a consequence of a reduced peripheral T4 deiodination. A pronounced reduction of T4 and thyroid stimulating hormone (TSH) concentrations was observed 24 h after application of the test solution by gavage. The luteinizing hormone (LH) decrease as well as the TSH decrease, which was pronounced in spite of reduced T4 and T3 levels indicate a central point of attack of the plant extract. Differences in the biological activity in dependence on the route of application may be explained e.g. by differences in absorption of plant constituents.

Animals↗

PubMed1998

Acute metabolic and endocrine effects of induced hypothermia in hemorrhagic shock: an experimental study in the pig.

BACKGROUND: Hypothermia is considered harmful in trauma patients. In surgery, hypothermia is occasionally used to reduce metabolism and protect the brain. Recent studies in animals have also shown protective effects of hypothermia in hemorrhagic shock. The aim of this study was to evaluate the metabolic and endocrine effects of induced hypothermia in hemorrhagic shock. METHODS: Half of the individually calculated blood volume was removed from 17 anesthetized piglets. They were then randomized to normothermia or hypothermia and followed for 4 hours after hemorrhage. RESULTS: In the hypothermic pigs, arterial PO2 increased from 10.3 +/- 0.7 to 16.4 +/- 0.9 kPa, but it remained unchanged in the normothermic group. The serum levels of potassium increased from 3.9 +/- 0.2 to 5.0 +/- 0.2 mmol/L in the normothermic group. In the hypothermic pigs, the potassium levels temporarily decreased from 3.8 +/- 0.1 to 3.0 +/- 0.1 mmol/L but then returned to baseline levels. The levels of serum catecholamines surged in both groups during hemorrhage. They remained elevated in normothermic pigs but declined in the hypothermic group. CONCLUSION: In porcine hemorrhagic shock, induced hypothermia increases arterial oxygen tension and stabilizes serum levels of potassium and catecholamines.

Animals↗

PubMedDate not supplied

Endocrine effects of early non-union of testis and epididymis and of cryptorchidism in the rat.

The aim of this study was to explore possible endocrine effects of early non-union of testis and epididymis. In 16 days old Sprague-Dawley rats the testis and epididymis were separated to the level of the inferior epididymis artery (non-union operation). Animals were killed at intervals from 30-58 days, and the plasma concentrations of total testosterone, total estrogens, LH, FSH and PRL were measured. The testes were studied by light microscopy. Groups of rats made cryptorchid and sham-operated rats were used as controls. Although their testes were scrotal, the non-union operated animals had testosterone and estrogen concentrations similar of cryptorchid animals, and significantly (p less than 0.05) lower than sham-operated animals. The LH- and FSH-concentrations were significantly (p less than 0.05) elevated suggesting a primary lesion in both Leydig- and Sertoli-cells. Towards puberty FSH increased in the non-union operated animals, while FSH values declined in the cryptorchid and sham-operated animals. These FSH-patterns probably reflect the existence of different pathogenic mechanisms in the non-union operated rats and the rats with cryptorchid testes.

Age Factors↗

PubMed1986

Clinical and endocrine effects of long-term hormonal contraception.

Clinical effectiveness and side effects of a biphasic oral hormonal contraceptive preparation (levonorgestrel /LNG/ 10 X 0.05 mg+ + 11 X 0.125 mg, ethinyl oestradiol /EO/ 21 X 0.05 mg) were compared with the effect of a classical high fixed dose combination pill (LNG 21 X 0.25 mg, EO 21 X 0.05 mg). The biphasic pill was used by 121 women during 1844 cycles, while the fixed dose pill was used by 142 women during 1940 cycles. In the comparison with the life table method, termination of pill use for medical reasons and loss to follow up proved to be significantly different in favour of the biphasic pill.

Contraceptives, Oral, Hormonal↗

PubMed1999

Endocrine effects, efficacy and tolerability of a 10.8-mg depot formulation of goserelin acetate administered every 13 weeks to patients with advanced prostate cancer.

OBJECTIVE: To determine the endocrine effects, efficacy and tolerability of a 10.8-mg depot formulation of Zoladextrade mark (goserelin acetate, Zeneca Pharmaceuticals, Wilmington, Delaware, USA), a luteinizing hormone-releasing hormone agonist analogue, when administration was extended from every 12 weeks to every 13 weeks in patients with advanced prostate cancer. PATIENTS AND METHODS: Between July 1995 and May 1996, 59 patients with either locally advanced (T3 or T4) or metastatic prostate cancer were enrolled in an open-label, multicentre trial. Primary efficacy endpoints were testosterone measurements, and assessments of prostate specific antigen (PSA) response, subjective and objective response. Quality of life (QoL) was a secondary efficacy endpoint. RESULTS: Mean testosterone concentrations decreased to < 0.3 microgram/L by week 4 and remained so for the duration of treatment. There were no statistically significant differences in mean testosterone levels between weeks 12 and 13, or weeks 25 and 26. Serum testosterone suppression was adequate in all 58 evaluable patients at week 13, and 51 of 52 (98%) patients at week 26. Of the 58 evaluable patients, 52 (90%) had a PSA response. A subjective response was recorded for six of 11 evaluable patients. Of 58 patients evaluable for objective response, 46 (79%) had a partial response, three (5%) had stable disease and nine (16%) had objective progression. Except for a significant (P=0.014) decrease in overall sexual interest, QoL was unchanged during therapy. The most common side-effects, regardless of causality, were hot flushes (67%), pain (31%) and pelvic pain (22%). Mild injection-site complaints occurred with only three of 221 (1.4%) depot injections. CONCLUSIONS: Zoladextrade mark 10.8-mg depot, administered every 13 weeks to patients with advanced prostatic cancer, is well tolerated, provides adequate suppression of serum testosterone and produces PSA, subjective and objective responses.

Aged↗

PubMed1984

Endocrine effects of the combination of megestrol acetate and tamoxifen in the treatment of metastatic breast cancer.

Six postmenopausal patients with metastatic breast cancer, who responded to megestrol acetate after 6 weeks of treatment, were treated with the combination of megestrol acetate and tamoxifen during the next 6 weeks. The study was oriented towards the endocrine effects of this combination since it was known from our previous studies that megestrol acetate induces suppression of serum gonadotropins and of the pituitary-adrenal axis, a decrease of peripheral concentration of SHBG and of estradiol, and an increase of basal and TRH-stimulated plasma prolactin concentration. Tamoxifen, on the other hand, produces a decrease of prolactin and gonadotropins, whilst estradiol remains unaffected. Although the role of prolactin in the growth of human breast cancer has not been elucidated yet and there is no unequivocal evidence that a decrease in plasma prolactin could be of benefit for treatment of metastatic breast cancer, we tested whether addition of tamoxifen to the treatment regimen eliminated megestrol acetate-induced hyperprolactinaemia. The results show that addition of tamoxifen to megestrol acetate treatment annihilated the hyper-response of prolactin to TRH stimulation, while basal prolactin levels remained unaffected. The negative effect on plasma gonadotropin concentration appeared to be amplified, while estradiol and cortisol were not affected and SHBG increased. The results of these endocrine investigations merit a further study, directed to antitumor effects of this combination modality.

Adult↗

PubMed1990

Analgesic, central, cardiovascular and endocrine effects of the enkephalin analogue Tyr-D.Arg-Gly-Phe(4NO2)-Pro-NH2 (443C81) in healthy volunteers.

443C81 is a synthetic enkephalin thought to act on peripheral opiate receptors. The analgesic, central, cardiovascular and endocrine effects of two i.v. doses of 443C81 were investigated in 12 healthy male volunteers. Its effects were compared with those of placebo and the classical opiate dipipanone given orally using a double dummy design. 443C81 produced dose-related analgesia; dipipanone 10 mg had a greater effect than the high dose 443C81. In contrast to dipipanone, 443C81 did not cause significant miosis or reduce minute volume on rebreathing CO2 and there was no evidence of sedation. Dry mouth was reported frequently and associated with reduced salivation after all active treatments. Both 443C81 and dipipanone increased circulating prolactin and growth hormone and reduced cortisol levels. This novel enkephalin appears to possess analgesic activity and some other properties of opiates but is devoid of clinically relevant narcotic effects.

Adult↗

PubMed2001

Metabolic and endocrine effects of metabolic acidosis in humans.

Metabolic acidosis is an important acid-base disturbance in humans. It is characterised by a primary decrease in body bicarbonate stores and is known to induce multiple endocrine and metabolic alterations. Metabolic acidosis induces nitrogen wasting and, in humans, depresses protein metabolism. The acidosis-induced alterations in various endocrine systems include decreases in IGF-1 levels due to peripheral growth hormone insensitivity, a mild form of primary hypothyroidism and hyperglucocorticoidism. Metabolic acidosis induces a negative calcium balance (resorption from bone) with hypercalciuria and a propensity to develop kidney stones. Metabolic acidosis also results in hypophosphataemia due to renal phosphate wasting. Negative calcium balance and phosphate depletion combine to induce a metabolic bone disease that exhibits features of both osteoporosis and osteomalacia. In humans at least, 1,25-(OH)2 vitamin D levels increase, probably through phosphate depletion-induced stimulation of 1-alpha hydroxylase. The production rate of 1,25-(OH)2 vitamin D is thus stimulated, and parathyroid hormone decreases secondarily. There is experimental evidence to support the notion that even mild degrees of acidosis, such as that occurring by ingestion of a high animal protein diet, induces some of these metabolic and endocrine effects. The possible role of diet-induced acid loads in nephrolithiasis, age-related loss of lean body mass and osteoporosis is discussed.

Acidosis↗

PubMed2006

Endocrine effects of oral dehydroepiandrosterone in men with HIV infection: a prospective, randomized, double-blind, placebo-controlled trial.

Dehydroepiandrosterone (DHEA) is commonly used by HIV-infected men, but its endocrine effects in this population are not well defined. We conducted an 8-week randomized, placebo-controlled trial to determine the effects of escalating doses (100-400 mg/d) of DHEA on the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes, and on a number of metabolic parameters in 69 HIV-positive men (31 in DHEA-treated group, 38 in placebo group). High-dose (250 microg) corticotropin and luteinizing hormone-releasing hormone stimulation tests were carried out in all subjects. Fifty-four subjects (26 in the DHEA-treated group and 28 in the placebo group) also underwent optional corticotropin-releasing hormone test, and 67 subjects (31 in DHEA-treated group and 36 in placebo group) underwent optional low-dose (1 microg) corticotropin stimulation test. All tests were performed at baseline and at the end of week 8. Repeated-measures analysis of variance was used to analyze the data. We observed significant increases in circulating levels of DHEA, DHEA-sulfate, free testosterone, dihydrotestosterone, androstenedione, and estrone, and a decline in the serum concentration of sex hormone-binding globulin in the DHEA-treated group but not in the placebo group (P < .001). There were no differences between the groups in other endocrine or metabolic parameters or in the results of the stimulation tests. In conclusion, oral DHEA therapy in HIV-positive men significantly increases circulating levels of DHEA and DHEA-sulfate, free testosterone, dihydrotestosterone, androstenedione, and estrone and suppresses circulating concentration of sex hormone-binding globulin. Long-term studies are needed to assess the clinical significance of these hormonal changes in subjects with HIV infection receiving oral DHEA therapy.

Administration, Oral↗