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Biomedical subjects

D T Krieger

Publications and source records attributed to D T Krieger.

At least 109 records · Page 6Linked to original sources
PubMed1978

Cyproheptadine treatment of Nelson's syndrome: restoration of plasma ACTH circadian periodicity and reversal of response to TRF.

Administration of cyproheptadine for four months to a patient with Nelson's Syndrome was associated with evidence of skin lightening, decreased plasma ACTH concentrations, return of a normal circadian periodicity of plasma ACTH concentrations, and lack of responsiveness of plasma ACTH concentrations to TRF administration, in contrast to the response seen in the untreated state.

Adrenocorticotropic Hormone↗
PubMed1978

Cortisol and androgen secretion in a case of Nelson's syndrome with paratesticular tumors: response to cyproheptadine therapy.

Bilateral paratesticular tumors were observed in a 32-yr-old man 14 yr after he developed a pituitary tumor after adrenalectomy for Cushing's disease (Nelson's syndrome). Plasma ACTH concentrations were markedly elevated (mean, 6350 pg/ml), but urinary free cortisol concentrations were low (27-31 micrograms/24 h). Catheterization revealed a spermatic to peripheral venous gradient for cortisol consistent with secretion of this steroid by the tumor. This was confirmed by decreased cortisol excretion after tumor excision. Serum androgen (testosterone, androstenedione, dihydrotestosterone, and dehydroepiandrosterone-sulfate) and progestin (progesterone and 17-hydroxyprogesterone) concentrations were decreased and did not decline further after tumor removal. These latter observations suggested that the paratesticular tumors did not secrete appreciable testosterone or any of its immediate precursors. Serum gonadotropin levels were also low. Cyproheptadine treatment resulted in a marked lowering of plasma ACTH concentrations (221-320 pg/ml). This was associated with an increase in both plasma LH and testosterone concentrations. These observations are consistent with the hypothesis that ACTH may directly affect LH and testosterone secretion.

Adrenalectomy↗
PubMed1977

Suprachiasmatic nuclear lesions do not abolish food-shifted circadian adrenal and temperature rhythmicity.

Daytime restriction of food and water availability in nocturnal animals phase shifts the circadian periodicity of plasma corticosteroid concentrations and body temperature. These shifted rhythms persist in animals with lesions of the suprachiasmatic nuclei who are arrhythmic under normal conditions. These findings suggest the existence of an additional "clock" that may be involved in the generation of the rhythm.

Animals↗
PubMed1977

Presence of corticotropin in brain of normal and hypophysectomized rats.

Immunoreactive and bioreactive corticotropin (ACTH-like) activities have been detected in the median eminence and remaining medial basal hypothalamus of both normal and hypophysectomized adult male rats: bioreactive ACTH (pg/100 mug of protein) 1028 in median eminence and 1289 in medial basal hypothalamus; immunoreactive ACTH (midportion ACTH antibody), 1554 in median eminence and 1887 in medial basal hypothalamus. By use of appropriate antibodies and bioassay, it was demonstrated that immunoreactivity was not due solely to alpha-melanotropin, which has previously been reported to be present in the brain of hypophysectomized animals. The Sephadex G-50 gel filtration patterns determined by immunoassay of column eluates obtained from hypothalamic extracts of normal or hypophysectomized animals were similar but were not identical to the pattern derived from whole pituitary. Immunoreactive (midportion ACTH antibody) ACTH concentrations (pg/100 mug of protein) of other central nervous system areas in normal animals were: cerebellum 34.3, cortex 46.3, thalamus 23.8, and hippocampus 116.3. The total amount of bioreactive ACTH present in the median eminence and medial basal hypothalamus is approximately 1% of that present in the pituitary. The present data suggest that such ACTH may have a diencephalic rather than pituitary origin and raise the question of the functional significance of such ACTH.

Adrenocorticotropic Hormone↗
PubMed1977

Corticotropin releasing factor distribution in normal and Brattleboro rat brain, and effect of deafferentation, hypophysectomy and steroid treatment in normal animals.

Corticotropin-Releasing Factor (CRF) activity was determined (dispersed pituitary cell assay) in rat median eminence (ME), various hypothalamic nuclei, as well as in entire median basal hypothalamus (MBH) and extra-hypothalamic areas. Highest concentrations were seen in ME, with decreased concentrations noted proceeding dorsally and cephalad from ME. Potency (NIAMDD HE-RP-1, ME reference extract, equivalent to 1.0) estimates were: ME-2.2; arcuate n.-0.88; dorsomedial n.-041; ventromedial n.-0.35; periventricular n.-0.24; hypothalamus-0.05; thalamus-0.01; cortex-0.005. Measurable, but lesser amounts, than in the above cited nuclei, were present in supraoptic and paraventricular nuclei. CRF activity was not measurable in preoptic area, septum, olfactory bulb, striatum, mesencephalon, pons, medulla or cerebellum. Complete hypothalamic deafferentation was accompanied by an increase in CRF activity/mug protein in ME and MBH, associated with decreased AM plasma ACTH and corticosterone concentrations. CRF-like activity in ME and MBH increased following hypophysectomy and after dexamethasone pretreatment. These findings indicate that CRF is mainly synthesized in the ME and surrounding area, and this source of CRF is sensitive to feedback effects and that extrahypothalamic inputs affect CRF release. Female animals had higher ME CRF content than did male animals. Homozygous and heterozygous Brattleboro rats had significantly less CRF in ME and MBH than did control animals, with significant differences also noted between homozygous and heterozygous animals.

Adrenal Cortex Hormones↗
PubMed1977

Presence of corticotropin in human placenta: demonstration of in vitro synthesis.

Immunoassayable (I) and bioassayable (B) ACTH activity is present in extracts of extensively washed human placental tissue and dispersed viable trophoblasts (Tr). Similar concentrations (I) (1.7-2.7 ng/g) are present in term placentas from elective cesarian section or vaginal delivery and from plancentas obtained by prostaglandin-induced abortion at 12, 15 and 18 weeks of gestation. Oral dexamethasone (8-12 mg) administered over an 8-48 h period prior to delivery does not significantly alter placental ACTH content. B-ACTH concentrations are 31-40% of I-ACTH. Sephadex G-50 filtration of term placental homogenates demonstrates two I-ACTH peaks, one eluting in the void volume and the other eluting in the region of synthetic hACTH1-39. When Tr are incubated in tissue culture medium, ACTH content of cells and of medium is significantly greater than pre-incubation levels.

Adrenocorticotropic Hormone↗
PubMed1977

Plasma ACTH and cortisol responses to TRF, vasopressin or hypoglycemia in cushing's disease and nelson's syndrome.

The response of plasma ACTH and/or cortisol concentrations to thyrotropin-releasing-factor (TRF), vasopressin, and insulin administration was determined in 5 patients with Nelson's syndrome and 12 patients with untreated Cushing's disease. TRF administration was associated with a mean increment of 267 pg/ml in plasma ACTH concentrations in patients with Nelson's syndrome, and of 42 pg/ml in patients with Cushing's disease. The increment in plasma cortisol concentrations in the latter group was 12 mug%. No ACTH or cortisol response was observed in normal subjects. Patients with Cushing's disease or Nelson's syndrome exhibited significantly greater increments in plasma ACTH concentrations in response to vasopressin administration (P less than .05, P less than .02 respectively) than did normal subjects; the increment in cortisol concentration was also greater, (P less than .05), in patients with Cushing's disease than in normal subjects. No significant difference was present between patients with Cushing's disease and Nelson's syndrome with regard to the magnitude of the ACTH response to vasopressin administration. In contrast, the increment in plasma cortisol and plasma ACTH concentrations following insulin induced hypoglycemia was significantly less in patients with Cushing's disease than seen in normal subjects, (P less than .001, P less than .05 respectively); while this stimulus was associated with a significantly greater increment in plasma ACTH concentrations in patients with Nelson's syndrome as compared to that seen in normal subjects, (P less than .01) and in patients with Cushing's disease (P less than .01). These findings indicate that pituitary function in patients with Nelson's syndrome is not autonomous and suggest the possibility that altered central nervous regulatory mechanism might play a role in the etiology of the pituitary tumors which are frequently associated with this syndrome. The TRF induced rise in plasm cortisol and ACTH concentrations in patients with Cushing's disease and Nelson's syndrome suggests the possibility of altered hypothalamic or pituitary receptors in such patients.

Adolescent↗
PubMed1977

Effect of bilateral superior cervical ganglionectomy (SCG) on pituitary adrenal function in the male albino rat.

The effect of sympathetic denervation (bilateral superior cervical ganglionectomy) on several aspects of pituitary adrenal function was studied in 250-300g rats. Group I=Sham-op, Group II=superior cervical ganglionectomy. (1) There was no significant difference between these groups in the plasma corticosterone (B) response to ether or immobilization stress or to ACTH administration. (2) Circadian periodicity of plasma B was determined by sequential (q.4h) tail vein sampling under LD (lights on 0800) off 2000) and under DL (lights on 2000, off 0800). Both groups showed similar peak and trough concentrations. Phase shifting occurred in both groups at day 11. (3) Compensatory adrenal hypertrophy of similar magnitude was present in both groups 10 days following unilateral adrenalectomy. These studies indicate that sympathetic input from the superior cervical ganglia is not involved in stress induced, circadian or some feedback aspects of pituitary adrenal function.

Adrenalectomy↗
PubMed1977

An improved bioassay for ACTH determination.

An improved method for the bioassay of ACTH has been developed using short-term culture of adrenal cell suspensions derived from intact rats. Six separate pools of adrenals were used and cells derived from the same pool were compared after acute dispersion and overnight culture. The ED50, defined as the concentration of ACTH required to produce half maximal steroidogenesis, for cultured cells was 35.4+/-2 pg/ml compared to 240+/-60 pg/ml for cells used immediately after dispersion. The minimum concentrations of ACTH necessary to produce a response significantly above basal levels were 0.98+/-.10 pg/ml and 12.1+/-3 pg/ml respectively. Response characteristics of the cultured cells were highly reproducible. The incubation volume employed in this study was 0.25 ml, so the ED50 expressed as dose of ACTH per tube was actually 8.8 pg for the cultured cells. Such sensitivity provides requisite methodology for the measurement of ACTH under varying physiological conditions.

Adrenal Glands↗
PubMed1976

The characterization of the ACTH produced by a primary pituitary tumour in a patient with Cushing's disease.

The nature of ACTH present in pituitary tumours associated with Cushing's disease has not been previously characterized nor correlated with the electron microscopic appearance. The present report describes the culture of tumour tissue obtained from a patient with a pituitary tumour associated with Cushing's disease, and the characterization of the ACTH content of tumour and media by bioassay, immunoassay, and Sephadex G-50 gel filtration. Electron microscopic studies were also performed. The pathological diagnosis was pituitary adenoma with basophilic PAS-positive granules. Electron microscopy showed uniformity of size and shape of the tumour cells, the presence of secretory granules of varying size and density, and disorganized tubular and vacuolar arrays of endoplasmic reticulum. The bioreactive ACTH content of the tumour was 0-29 mug/g, which is markedly below that seen in the normal pituitary, but within the range reported for ectopic ACTH-producing tumours. Immunoreactive ACTH when measured by a C-terminal antibody was five-fold higher than when measured by an N-terminal antibody; the latter gave a value of 1-24 mjg/g. On Sephadex G-50 gel filtration, 9% of the N-terminal immunoreactivity was present in the Vo fraction ('big' ACTH). This latter fraction had a greater percentage of bioreactivity (28%) than previously reported for this molecular species. Analysis of the tumour culture medium revealed a variation in molecular size similar to that seen in the tumour, although the percentage of ACTH of large molecular size was greater, suggesting increased secretion of a possible 'prohormone' by the tumour. Plasma ACTH was characterized by a 2:1 ratio of immunoreactivity (N-terminal) to bioreactivity, and a 4:1 ratio of C-terminal/N-terminal immunoreactivity. This report also appears to be the first of successful short-term tissue culture of a primary ACTH-producing tumour. The granule size was considerably larger than that reported for normal pituitary ACTH-containing cells.

Adenoma↗
PubMed1976

Circadian periodicity of epidermal growth factor and its abolition by superior cervical ganglionectomy.

The concentration of epidermal growth factor (EGF) in mouse submaxillary gland displays a circadian variation, which can be phase-shifted by light-dark reversal, and which is abolished by superior cervical ganglionectomy (SCG). Such circadian variation persists in fasted animals. Peak concentrations occur during light hours, trough concentrations during dark, although peak concentrations in female animals occur 8 h in advance of the time when they are seen in male animals. The nocturnal fall can be reversed by a one hour exposure to light presented during the normal dark period. SCG does not abolish the increase in submaxillary gland EGF concentrations to levels characteristic of the normal male that is seen following testosterone administration to female mice (who normally exhibit much lower EGF concentrations). Plasma EGF concentrations do not exhibit a ciradian variation.

Animals↗