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Biomedical subjects

S M Webb

Publications and source records attributed to S M Webb.

At least 73 records · Page 4Linked to original sources

Rhythms in pineal immunoreactive somatostatin in the Syrian hamster, mouse, and gerbil.

Immunoreactive somatostatin (IRS) has been previously demonstrated in the pineal gland of different rodent species, and we observed a 24-hr rhythm in rats. Recent data suggest that the peptide may represent a neurotransmitter in the so-called peptidergic nerves of the central, pinealopetal innervation of the epiphysis, which may modulate the activity and secretion of the gland. We investigated whether 24-hr changes of pineal IRS content occurred in Syrian hamsters, gerbils, and mice. Adult males, kept in a 14:10 LD photoperiod, were decapitated at 4-hr intervals throughout a 24-hr period. Pineals and median eminences were analyzed for IRS by radioimmunoassay. No significant changes in the median eminence content of IRS with time was observed. As previously described in rats, a statistically significant rhythm of IRS was observed in the pineal of hamsters and mice, with a peak at 2000 hr (mice 51.7 +/- 5 pg/pineal; hamsters 26.3 +/- 4.6) and a nadir at 2400 hr (mice 30.8 +/- 1.4) or 0400 hr (hamsters 8.6 +/- 1). However, in the gerbil pineal IRS content remained unchanged throughout the period of study. Since the three species examined have very different melatonin cycles, it is suggested that the melatonin and IRS rhythms are unrelated and independently regulated events within the pineal gland.

Animals↗

Androgenic control of immunoreactive somatostatin in the Harderian gland of the Syrian hamster.

Harderian glands of Syrian hamsters contained measurable levels of immunoreactive somatostatin. After an extraction procedure, serial dilutions of tissue were assayed and showed parallelism in the displacement curve with dilutions of purified somatostatin standard in the radioimmunoassay. Somatostatin concentrations were higher in female hamsters (10.0 +/- 2.1 ng/mg protein) than in males (2.6 +/- 0.4 ng/mg protein). Castrated males had somatostatin values in the range of females (12.4 +/- 2.3 ng/mg protein) at 1 month after gonadectomy. Testosterone implants prevented the rise of Harderian gland somatostatin in castrated males. Gonadectomized males had lower somatostatin content in the gland than did control males (1.0 +/- 0.2 ng/mg protein) at 2 months after castration. Somatostatin values in females were unaffected by gonadectomy, but there were variations during the oestrous cycle, with a nadir detected at dioestrus-1 and maximal values coincident with the day of the ovulation.

Androgens↗

Pregnancy-induced changes in prolactinomas as assessed with computed tomography.

Seven women with prolactin-secreting pituitary microadenomas and three with persistent hyperprolactinemia after surgical adenomectomies were evaluated with computed tomography to assess the effect of pregnancy on the volume of pituitary prolactinomas and hyperfunctioning pituitary tissue. In one patient a microadenoma enlarged to become a macroadenoma. Tumor enlargement occurred in the remaining six patients with microadenomas. None of the patients with previously resected adenomas exhibited hypertrophy of residual pituitary tissue or tumor recurrence after pregnancy.

Female↗

Endocrine aspects of pituitary stalk enlargement.

Four patients with various endocrine deficiencies of a predominantly hypothalamic nature are described, in whom computed topographic scans demonstrated pituitary stalk enlargement. In one, a disseminated papular skin eruption with regional pleomorphism and spontaneous regression appeared 4 years after the development of the initial symptoms of diabetes insipidus, and led to a diagnosis of xanthoma disseminatum, a rare type of histiocytosis. It is suggested that this patient's endocrine dysfunction is also due to histiocytic involvement of the hypothalamus and/or pituitary stalk. In view of the prolonged lapse of time between the initial endocrine manifestations and the eventual diagnosis, even though no cause is apparent in the other three patients, it is suggested that close follow-up be carried out to rule out such a possibility in patients with this endocrine-radiological entity.

Adolescent↗

Circulating immunoreactive somatostatin in gastrointestinal diseases. Decrease after vagotomy and enhancement in active ulcerative colitis, irritable bowel syndrome, and duodenal ulcer.

The main source of circulating immunoreactive somatostatin (IRS) seems to be the gastrointestinal tract. We therefore investigated plasma IRS in patients with various gastrointestinal diseases. Mean basal IRS oscillated between 46 and 73 pg/ml. A postprandial rise was observed in all patients and age-matched controls. However, the increment was significantly higher in patients with duodenal ulcer (159 +/- 20 pg/ml), active ulcerative colitis (176 +/- 17 pg/ml), and irritable bowel syndrome (194.4 +/- 20.4 pg/ml). Patients with duodenal ulcers who underwent vagotomy showed a decreased postprandial increment (107 +/- 10 pg/ml) when compared with active duodenal ulcer patients. No difference was demonstrable between controls and individuals with gastric ulcer, and patients with inactive ulcerative colitis. These results suggest that vagal innervation plays a role in postprandial IRS stimulation, whereas gastric hyperacidity, acute lesions of the colonic mucosa, and hypermotility of the gastrointestinal tract are associated with an exaggerated postprandial IRS response. Since somatostatin is known to influence many gastrointestinal functions, these variations in circulating IRS concentrations may be of pathophysiologic importance.

Adult↗

Influence of delta-sleep inducing peptide on melatonin synthesis in the rat pineal gland.

The influence of delta-sleep inducing peptide (DSIP) on rat pineal N-acetyltransferase (NAT) activity and melatonin levels was examined. Young adult rats received an injection of either saline or DSIP (either 15, 30 or 60 nmol/kg) at 20:00 h, immediately before lights out. DSIP at a dose of 15 nmol/kg significantly retarded the nighttime rise of pineal NAT activity and melatonin levels at 3 h into the dark phase. At the other two nocturnal time points (01:00 and 03:00 h) and the following morning (08:00 h) pineal NAT activity and melatonin levels were similar in all groups. The results confirmed a short-lived, dose-specific effect of DSIP on serotonin metabolism in the rat pineal gland.

Animals↗

Cysteamine effects on somatostatin, catecholamines, pineal NAT and melatonin in rats.

The thiol reagent cysteamine was administered to adult male rats with the aim of investigating its effect on different neural and pineal components. As expected, immunoreactive somatostatin decreased in the median eminence (ME) (p less than 0.05) and gastric antrum (p less than 0.05) after cysteamine; however, no significant change was observed in the pineal IRS content after drug treatment. A decrease in norepinephrine was observed in the ME (p less than 0.001), hypothalamus (p less than 0.001) and pineal gland (p less than 0.05), together with a rise in ME (p less than 0.005) and hypothalamic dopamine (p less than 0.005) content; these results are consistent with a dopamine-beta-hydroxylase inhibiting effect of cysteamine. No effect was observed on hypothalamic serotonin and 5-hydroxyindole-acetic acid content. Pineal N-acetyltransferase (NAT) activity was significantly higher (p less than 0.05) after cysteamine than after saline, but no statistically significant effect was observed on pineal melatonin content. The mechanism involved in the NAT rise is presumably not related to the known stimulatory effect of norepinephrine, which fell after cysteamine. It is suggested that cysteamine may act at an intracellular level, inhibiting NAT degradation, an effect demonstrated in vitro and thought to be related to a thiol:disulfide exchange mechanism.

Acetyltransferases↗

ACTH and prolactin deficiency.

A 35 year old woman suffering from ACTH and prolactin (Prl) deficiency is described. Her symptoms of adrenal insufficiency appeared gradually after her first pregnancy in 1970; however, she conceived twice more and delivered healthy babies in 1972 and 1974, which she could not breast feed due to lack of milk. During an episode of pneumonia in 1977 she suffered acute adrenal insufficiency, after which she began treatment with hydrocortisone. Her pituitary reserve for TSH, GH, LH and FSH was normal, but her ACTH and Prl levels were undectable and did not respond to acute iv challenges of corticotrophin-releasing factor (CRF) and TRH, respectively. Autoantibodies, including antilactotroph titres, were negative, except for a positive pituitary immunofluorescence to ACTH. There was also no ACTH stimulation to a prolonged infusion of CRF followed by an acute iv bolus. These results, together with the gradual onset of symptoms which worsened after each pregnancy, suggest a possible autoimmune aetiology of her pituitary ACTH and Prl deficiencies.

Adrenocorticotropic Hormone↗

Deficiency of immunoreactive somatostatin in the median eminence of Snell dwarf mice.

Snell dwarf mice (dw/dw) are characterized by a genetically determined, congenital lack of pituitary GH, TSH and prolactin. Given that hypothalamic somatostatin is involved in the regulation of pituitary GH and TSH release, it was decided to investigate the content of immunoreactive somatostatin (IRS) in the median eminence of dw/dw and phenotypically normal mice of the same strain. The content of IRS in the pyloric antrum and pineal gland of these animals was also examined. The effects of ovariectomy and of hyperprolactinemia (induced by a pituitary graft under the kidney capsule) on the median eminence content of IRS were also studied in both normal and dwarf mice. Median eminence IRS content was significantly lower in the dw/dw (23.6 +/- 1.8 ng) than in normal mice (57.4 +/- 7.1 ng); no difference was found in the pyloric IRS content of dw/dw (16.9 +/- 1.6 ng/mg of protein) and normal animals (13.8 +/- 1.9 ng/mg of protein), nor in the pineal content of IRS (639.4 +/- 64.4 pg/gland in the dw/dw; 732 +/- 265 pg/gland in normals). Neither ovariectomy nor hyperprolactinemia were found to affect the IRS content in the tissues studied in normal or dwarf mice. Treatment of an additional group of 9 dwarf mice with L-thyroxine (L-T4 2 micrograms/48 h. s.c. for 2 weeks) significantly increased the animals weight (10.2 +/- 0.4 g versus 7.4 +/- 0.3 g) and produced maturation of facial features; however, it did not change the IRS content in any of the tissues studied. It is concluded that the content of IRS in the median eminence of mice with a congenital lack of GH, TSH and prolactin is significantly reduced and that this is unlikely to be related to the deficiency of thyroid hormones in these animals.

Animals↗

Hormonal modulation of pineal melatonin synthesis in rats and Syrian hamsters: effects of adrenalectomy and corticosteroid implants.

Pineal levels of tryptophan, 5-hydroxytryptophan, serotonin, N-acetylserotonin, melatonin, 5-hydroxyindoleacetic acid and the activities of the enzymes N-acetyltransferase and hydroxyindole-O-methyltransferase were determined in male albino rats and Syrian hamsters that were implanted with the appropriate corticosteroid or adrenalectomized two weeks earlier. Melatonin content and NAT activity were increased at 4 hours (during darkness) in adrenalectomized hamsters; conversely, no alterations in melatonin levels were observed in either adrenalectomized or implanted rats. It is suggested that the changes in adrenal function probably have a minor influence on pineal melatonin production.

Adrenal Cortex Hormones↗

Nighttime immunoreactive somatostatin content of the median eminence in hypo- and hyperthyroid rats.

The median eminence content of immunoreactive somatostatin (IRS) was measured by radioimmunoassay in 107 male albino rats, who were either hypothyroid after surgical thyroidectomy (N = 38), hyperthyroid following a subcutaneous implant of 5 mg of L-thyroxine (N = 36), or otherwise untreated (N = 33). Thyroid function was assessed by determining plasma levels of T4 and TSH from trunk blood obtained at the time of decapitation. Subgroups of animals from the 3 groups were killed either before (1800 hr), during (2200, 0200, 0400 hr), or after the dark portion of their 14:10 LD photoperiod. Although no changes in median eminence IRS content were found throughout the period of study within any of the 3 groups, hypothyroid animals (297.23 +/- 13.47 ng per ME; 620.41 +/- 58 ng IRS/mg protein) had a significantly lower median eminence IRS concentration than untreated rats (355.86 +/- 16.55 ng of IRS per ME, P less than 0.01; 906.86 +/- 96.38 ng IRS/mg protein, P less than 0.05) and hyperthyroid animals (384.12 +/- 14.67 ng per ME, P less than 0.001; 874.1 +/- 104.5 ng IRS@mg protein, P less than 0.05). It is concluded, that the feedback of thyroid hormones on the hypothalamic-pituitary axis during thyroid hormone excess in vivo, contrary to what occurs in hypothyroidism, is probably independent of hypothalamic somatostatin.

Animals↗

Photoreceptor damage and eye pigmentation: influence on the sensitivity of rat pineal N-acetyltransferase activity and melatonin levels to light at night.

The threshold of light irradiance capable of inhibiting nighttime pineal serotonin N-acetyltransferase (NAT) activity and melatonin content, and the importance of intact photoreceptors and eye pigmentation on these changes, were investigated in the rat. Groups of intact albino and black-eyed rats and albino animals with light-induced photoreceptor damage were studied in the dark period before, and after 15 and 30 min of exposure to either 0.0005, 0.175 or 3.33 microW/cm2 irradiance of light. In animals with photoreceptor damage, the sensitivity of the pineal gland to light decreased so that only the highest irradiance tested (3.33 microW/cm2) was capable of totally inhibiting pineal NAT activity and melatonin levels. In one study, pineal NAT and melatonin levels in intact albino rats were inhibited by all three irradiances studied. In a second experiment, albino and black-eyed animals behaved identically, only responding with a depression in pineal NAT and melatonin after exposure to light irradiances of either 0.175 or 3.33 microW/cm2. In conclusion, the lowest irradiance of cool white light capable of inhibiting pineal NAT and melatonin in albino rats is around 0.0005 microW/cm2. At the irradiances studied, photoreceptor damage influences the response of pineal NAT and melatonin to acute light exposure at night. On the other hand, eye pigmentation does not seem to have a major effect on the nighttime inhibition of the pineal by light.

Acetyltransferases↗

Circulating immunoreactive somatostatin in man. Effect of age, pregnancy, growth hormone deficiency and achlorhydria.

Plasma immunoreactive somatostatin (IRS) levels were measured fasting at 09.00 h in groups of adult individuals and children of different ages, as well as in pregnant women, in patients with pernicious anaemia documented to be achlorhydric, and in children with growth hormone deficiency. There was a gradual rise in the mean level of IRS from the third decade (mean 35.8 +/- 3.8 pg/ml), which reached significance at the seventh (61.1 +/- 8.4 pg/ml), eighth (66.7 +/- 5 pg/ml) and ninth decade (82.6 +/- 13.8 pg/ml). No change was observed in the second 28.3 +/- 3.8 pg/ml) and third (31.1 +/- 3.2 pg/ml) trimester of pregnancy when compared with matched, non-pregnant controls (29.7 +/- 2.2 pg/ml); however, the children aged under 2 years (69.6 +/- 11.2 pg/ml) had significantly higher values than the eldest group (12 to 16 years old) (46.3 +/- 7.2 pg/ml) (P less than 0.05). In achlorhydric patients, basal (27.2 +/- 3.7 pg/ml; P less than 0.01) and postprandial IRS (42.8 +/- 7.7 pg/ml; P less than 0.001) was significantly lower than in a matched, normal control group (basal 59.4 +/- 7.2; postprandial 132.1 +/- 26.3 pg/ml). Growth hormone deficiency was not associated with any differences in circulating IRS, basally or after insulin hypoglycaemia, when compared with values in normal children.(ABSTRACT TRUNCATED AT 250 WORDS)

Achlorhydria↗

Hormonal modulation of cyclic melatonin production in the pineal gland of rats and Syrian hamsters: effects of thyroidectomy or thyroxine implant.

Night-time pineal levels of tryptophan, 5-hydroxytryptophan, serotonin, N-acetylserotonin, melatonin, 5-hydroxyindoleacetic acid and the activities of the two enzymes N-acetyltransferase and hydroxyindole-O-methyltransferase involved in the cyclic production of melatonin were determined in male albino rats and Syrian hamsters that were implanted with thyroxine or thyroidectomized two weeks earlier. Both treatments depressed nocturnal pineal melatonin content in rats and hamsters. The cause of this depression is not known, although minor alterations in the substrates and the enzymes involved in melatonin production were observed. The data suggest that alterations in thyroid hormone levels may increase the release of nocturnal melatonin from the pineal, thereby allowing less to accumulate in the gland.

5-Hydroxytryptophan↗