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[Changes of growth hormone-releasing factor (GRF) in rat peripheral blood--effect of hypophysectomy].

Accumulating evidence has emerged indicating that growth hormone-releasing factor (GRF) is present not only in the hypothalamus but in other tissues as well. Using highly specific and sensitive radioimmunoassays and immunoaffinity chromatography, we found low but clearly measurable GRF-like immunoreactivity (GRF-LI) levels in rat peripheral plasma. In order to verify the immunological findings, the peripheral plasma GRF-LI was characterized using fast protein liquid chromatography. The immunological peak was eluted at the position of synthetic rat GRF standard. These findings demonstrate that rat peripheral plasma GRF is immunologically and chromatographically indistinguishable from authentic rat GRF. Moreover, we performed studies with hypophysectomy to assess whether peripheral plasma GRF-LI changes in physiological status. At 4 weeks after hypophysectomy, there was a significant (p less than 0.05) increment in the rat plasma GRF-LI [12.4 +/- 0.5 (+/- SEM) pg/ml in hypophysectomized rats as opposed to 5.8 +/- 0.4 pg/ml in sham-operated control rars]. On the other hand, hypothalamic GRF-LI fell significantly as compared that of controls (36.1 +/- 1.0 vs. 78.3 +/- 3.0 pg/mg wet weight tissue). A similar pattern of changes in GRF-LI at 10 weeks after hypophysectomy was also revealed. The source of rat peripheral plasma GRF has not yet been elucidated. Our results, however, may suggest that GRF levels are modulated by negative feedback at the level of the hypothalamus by a pituitary factor, presumably growth hormone (GH) and that hypothalamic GRF release exceeds its synthesis in hypophysectomized rats.

Animals↗

Effect of hypophysectomy on hypothalamic somatostatin content in rats.

The effect of hypophysectomy on the hypothalamic somatostatin content was examined in rats. Somatostatin content in the acid extract of the pituitary stalk and the median eminence tissue (SME) was measured by specific radioimmunoassay. In young male rats, the mean somatostatin content in SME was 63.9+/-5.0 ng. Two weeks after hypophysectomy, it was reduced significantly to 34.4+/-3.3 ng. The result may indicate that the elimination of feedback actions of GH and/or TSH on the hypothalamus led to the decreased synthesis and/or the release of somatostatin. However, the possibility that structural changes in the pituitary stalk and the median eminence tissue ensued after hypophysectomy resulted in the depletion of somatostatin cannot be ruled out.

Animals↗

Short- and long-term effects of hypophysectomy and unilateral ovariectomy on ovarian follicular populations in sheep.

The effects of hypophysectomy and unilateral ovariectomy on the total number of follicles with greater than 3 layers of granulosa cells were determined at 4 and 70 days following treatment. The population of preantral follicles (less than 0.23 min diam.) was found to be under the control of gonadotrophins but such control was only evident on a long-term basis. At 70 days after unilateral ovariectomy there was a large increase in the number of preantral follicles but at 70 days after hypophysectomy there was a large decrease. The population of antral follicles (greater than 0.23 mm diam.) was under the immediate control of gonadotrophins. By 4 days after hypophysectomy all large antral follicles had become atretic and the number of antral follicles was further decreased at 70 days after treatment. At 70 days after unilateral ovariectomy there was an increase in the number of antral follicles. The follicular growth rates at 70 days following treatment were decreased in hypophysectomized ewes but increased in ewes after unilateral ovariectomy.

Animals↗

Responsiveness of growth hormone release in acromegalics after irradiation or hypophysectomy.

Effects of X-ray irradiation to the pituitary and transfrontal hypophysectomy were evaluated on the responsiveness of plasma growth hormone (GH) to exogenous stimuli in 8 patients with acromegaly. As exogenous stimuli, arginine, TRH, LH-RH and L-dopa were administered. In 2 out of 3 patients treated with Liniac irradiation, the responsiveness to arginine was essentially unchanged, while in the third patient positive response to arginine disappeared after therapy. Of 2 patients who received a combination of hypophysectomy and Liniac irradiation, the responsiveness to arginine, TRH, LH-RH and L-dopa did not change in 1 patient, but in the other it was observed that negative response to L-dopa became positive after the treatment, remaining the unchanged responsiveness to arginine, TRH, and LH-RH. In 3 hypophysectomized patients, little change in responses to the above 4 stimuli was observed. In summary, out of 22 pairs of responses (pre- and post-therapy) examined 20 were not altered. In 11 pairs of responses (pre- and post-irradiation) particularly, 10 were essentially unchanged. It might be concluded that the responsiveness of GH to exogenous stimuli in acromegalics would not be affected by irradiation or transfrontal hypophysectomy.

Acromegaly↗

Persistence of impaired PRL responses to sulpiride in patients with PRL secreting pituitary adenomas after successful hypophysectomy.

TRH, arginine, L-dopa, and sulpiride tests for PRL secretion were carried out in 18 control subjects and 20 patients with pituitary PRL-secreting adenomas before and after hypophysectomy. After the hypophysectomy PRL levels fell to normal ranges in 9 cases (categorized as Group I), and remained high in 11 other cases (categorized as Group II). After the operation, there were no alterations of PRL responsiveness to TRH, arginine, or to L-dopa in terms of percent change from the basal value, in either Group I or Group II. No significant differences were found in PRL responses to the above three agents between operated Group I patients and normal subjects even when expressed in absolute values. On the other hand, the PRL responses to sulpiride in both Groups I and II improved markedly after the hypophysectomy, but the absolute response in operated Group I patients was still lower than that in normal subjects. The mean PRL value in operated Group I (mean +/- S.E., 13.2 +/- 0.8 ng/ml, n = 9) was significantly (p less than 0.01) higher than in normal subjects (5.1 +/- 0.4 ng/ml, n = 18). It is concluded 1) that even in hypophysectomized normoprolactinemic patients the circulating PRL may originate mainly from the residual tumor cells, and 2) that the sulpiride test is useful to detect the abnormalities of hypothalamo-pituitary axis in operated patients with PRL-secreting adenomas, whereas TRH, arginine, and L-dopa tests are less useful for such purposes.

Adenoma↗

The effects of hypophysectomy and of bovine growth hormone on the responses to testosterone of prostate, preputial, Harderian and lachrymal glands and of brown adipose tissue in the rat.

The relative responses to testosterone of the prostate, preputial, Harderian, and lachrymal glands, the seminal vesicles and the brown adipose tissue, have been compared in litter-mate, castrated and hypophysectomized-castrated rats, with or without treatment with bovine GH. The responses of both prostate and preputial glands, though not the seminal vesicles, were reduced by hypophysectomy, and restored by GH. Growth hormone had some independent action on the preputial glands, but most of its effect was synergistic with testosterone. The respinse of brown adipose tissue to testosterone was similarly reduced by hypophysectomy, but was not restored by the GH. The weights of the Harderian and lachrymal glands were not affected by castration, but they were considerably reduced by hypophysectomy. Growth hormone had a slight restorative effect on the Harderian glands, but none on the lachrymal glands.

Adipose Tissue, Brown↗

Effect of fetal hypophysectomy on the localization of the catecholamine biosynthetic enzymes and enkephalins in the adrenal medulla of the fetal sheep.

We have investigated the effect of fetal hypophysectomy on the localization of dopamine B-hydroxylase (DBH), phenylethanolamine N-methyltransferase (PNMT) and enkephalin-containing peptides in the fetal sheep adrenal, using immunocytochemical techniques. Staining with anti-DBH was observed throughout the adrenal medulla in the intact (140-146 days of gestation) and hypophysectomized fetal sheep (147-164 days of gestation) and the newborn lamb (10-12 days after birth). In the adrenal medulla of the late-gestation intact fetal sheep and newborn lamb, positive staining with anti-PNMT was observed in the peripheral rim of medullary cells adjacent to the adrenal cortex. After hypophysectomy, there was intense positive staining with anti-PNMT in the peripheral adrenal medullary cells and a small and variable proportion of central adrenal medullary cells were stained with anti-PNMT. In the adrenal gland of the intact fetal sheep and the newborn lamb, there was intense staining with anti-enkephalin in the peripheral rim of adrenal medullary cells. Staining with anti-enkephalin was less intense in the central medullary cells of the adrenal gland of the intact fetal sheep and the 10- to 12-day-old newborn lamb, and many unstained central medullary cells were present. After hypophysectomy, intense positive staining with anti-enkephalin was observed throughout the entire fetal adrenal medulla. Therefore, the fetal pituitary, either directly or indirectly through the adrenal cortex, plays a role in regulating the pattern of localization of both PNMT and enkephalin in the fetal sheep adrenal.

Adrenal Medulla↗

Cytosolic glucocorticoid receptors in the porcine lung during development and after hypophysectomy or thyroidectomy.

The ontogeny of fetal lung glucocorticoid receptors and their regulation by the fetal pituitary, adrenal and thyroid gland during lung maturation were investigated. Sites with a specificity typical of glucocorticoid receptors were detectable in lung cytosol, with the order of potency of steroids being dexamethasone greater than cortisol greater than corticosterone greater than 11-deoxycorticosterone greater than progesterone greater than 17 alpha-hydroxyprogesterone greater than oestradiol-17 beta congruent to testosterone congruent to androstenedione congruent to oestrone. The binding affinity for [3H]dexamethasone was high (Kd = 0.23-0.60 nmol/l) and showed an age-related decrease during the perinatal period when cortisol levels were high. After charcoal treatment of the cytosol, however, a decrease in binding affinity was not as clearly evident. The Kd decreased following hypophysectomy of fetuses; thyroidectomy had no significant effect. The concentration of glucocorticoid receptors was high from day 82 to day 100 of gestation (1437 fmol/mg protein) and declined progressively to a lower value at term and following birth (660 fmol/mg protein). Hypophysectomy, but not thyroidectomy, prevented the age-related decline in receptor concentration. Lung glycogen content declined with fetal ageing in association with increases in plasma concentrations of cortisol and thyroxine and with changes in Kd and Bmax, but appeared to be more closely associated with concentrations of thyroxine. Hypophysectomy of fetuses decreased concentrations of both cortisol and thyroxine and prevented the depletion of lung glycogen content. Preliminary results from thyroidectomized fetuses showed decreases in plasma thyroxine and lung glycogen content compared with day-82 fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Acellular dermal allograft for sellar reconstruction after transsphenoidal hypophysectomy.

Obliteration of the sphenoid sinus using fat is often used after transsphenoidal hypophysectomy. The morbidity of this approach includes donor site complications, fat necrosis, and delayed mucocele formation. As obliteration with fat is intended to prevent cerebrospinal fluid (CSF) leakage, an alternative for this technique would be techniques used for CSF rhinorrhea repair. Instead of sinus obliteration, these defects are repaired with fascial autografts, which are unfortunately associated with donor site complications. To avoid sinus obliteration and donor site complications, we have reconstructed the sella with acellular dermal allograft in lieu of sinus obliteration. Transsphenoidal hypophysectomy was performed under combined microscopic and endoscopic visualization. For closure, the sellar anterior wall was reconstructed with acellular dermal allograft, septal cartilage/bone autograft, and fibrin glue. The sinus mucosa was then draped over the reconstruction and held in place with microfibrillar collagen hemostat slurry. The sphenoid sinus was not obliterated. Postoperatively, all patients underwent serial nasal endoscopy. Thirteen patients underwent the procedure as described for removal of pituitary adenoma. Postoperative discomfort and pain were minimal. Intraoperative CSF leaks were identified in five patients; none of these patients experienced a postoperative CSF leak. The microfibrillar collagen hemostat was cleared by sphenoid mucociliary clearance. One patient developed acute sphenoid sinusitis several weeks after surgery; this patient did not develop meningitis. One postoperative CSF leak occurred in an obese patient, in whom an intraoperative CSF leak was not identified; this leak resolved with bedrest and delayed lumbar drainage alone. Sellar reconstruction with acellular dermal allograft may eliminate the need for sphenoid sinus obliteration after transsphenoidal hypophysectomy. Acellular dermal allograft sellar reconstruction ultimately provides for an aerated, functioning sphenoid sinus without increased CSF leak risk or potential donor site morbidity.

Female↗

Effect of hypophysectomy and growth hormone on serum and antral gastrin levels in the rat.

The effects of hypophysectomy and subsequent replacement therapy with growth hormone on serum and antral gastrin levels was investigated in both fasted and nonfasted pair-fed rats. Hypophysectomy caused a 57% decrease in serum and 47% decrease in antral gastrin content in 18-hr fasted animals. In nonfasted animals, hypophysectomy resulted in a 42% fall in serum gastrin and a 76% fall in antral gastrin. Animals were given injections of growth hormone over a 10-day period, then fasted 16 to 18 hr before being killed. Doses of 100 to 200 mug per 100 g of body weight were ineffective, but a dose of 500 mug per 100 g was sufficient to restore completely serum gastrin levels to intact control values. In nofasted rats this same dose raised serum gastrin to intact levels and increased antral gastrin significantly over hypophysectomized levels, but did not increase it to control values. When given to pair-fed intact animals, growth hormone caused slight but not significant elevations in serum and antral gastrin. The effect of growth hormone on gastrin secretion and /or synthesis may be a significant physiological factor in the regulation of normal gastrointestinal function and growth.

Animals↗

Hypophysectomy or adrenalectomy; their use in management of advanced malignant disease as observed in clinics in Europe.

The dependence of cancer of the breast and prostate gland upon sex hormones has led to an attack on this problem by way of adrenalectomy with castration or by hypophysectomy when hormone treatment has failed. The survival period of patients who have had adrenalectomy or hypophysectomy has been prolonged by use of cortisone. The risk of either operation is reasonable and maintenance of life on cortisone is simple. The results are encouraging, with a tendency in favor of hypophysectomy. It seems justifiable to advise operation at an early stage of the disease.

Adrenal Glands↗

Effects of hypophysectomy and in vivo administration of ACTH or dexamethasone on the level of ACTH receptor mRNA in adrenal glands and adipose tissues of mice.

OBJECTIVE: In rodents, ACTH induces steroidogenesis in the adrenal cortex and also lipolysis in adipose tissues via the sole specific receptor for ACTH. Up-regulation of the ACTH receptor (ACTH-R) mRNA by ACTH was found to be evident in adrenocortical cells. However, a role of in vivo ACTH on ACTH-R mRNA expression in the adrenal cortex is not well understood. In addition, so far less attention has been also paid to the regulation of ACTH-R expression in adipose tissues. We investigated the effects of hypophysectomy and in vivo administration of ACTH or dexamethasone on the level of ACTH-R mRNA in the adrenal gland and adipose tissues of mice. METHODS: ACTH mRNA in the adrenal glands and epididymal adipose tissues of mice sacrificed 10 days after hypophysectomy or sham operation, and 24 hours after ACTH-Z (2 IU i.m.) or physiological saline solution (PSS) injection, and also 3-days after dexamethasone (300 microg/day i.m.) or PSS administration was analysed by Northern blot, and intensities of autoradiographic bands were quantified. RESULTS: In the adrenal gland, in vivo administration of ACTH-Z significantly increased the level of ACTH-R mRNA to 342% of control values, but in vivo administration of dexamethasone or hypophysectomy induced no significant alteration of ACTH-R mRNA. In adipose tissues, these conditions did not significantly alter the level of ACTH-R mRNA. CONCLUSION: Low circulating ACTH may not be a substantial factor for ACTH-R gene expression in the adrenal gland, but a high level of in vivo ACTH dose up-regulated the expression. A different regulation of ACTH-R gene expression exists in the adrenal cortex and adipose tissues of mice.

Adipose Tissue↗

Effect of hypophysectomy and growth hormone substitution on red blood cell morphology and filterability in rats.

Growth factors, including insulin, are known to stimulate erythroid cell formation in vitro. This somatotrophic effect of insulin might be involved in blood abnormalities in diabetes mellitus. We therefore investigated whether growth hormone (GH) affects the morphology or filterability of circulating red blood cells (RBCs) in hypophysectomized rats. After hypophysectomy, rats became anemic with a decrease in hematocrit, hemoglobin concentration, RBC count, and reticulocytes. The RBC membrane area was enlarged, giving an increased area-to-volume ratio compared with the control RBCs. The calculated minimum cylindrical diameter (MCD) and resistance to initial folding of the RBC decreased after hypophysectomy, and was confirmed by an enhanced filtration of RBCs through 3 microns Nucleopore membranes. The number of filter clogging particles was also lower in hypophysectomized rats than in control rats. Substitution for 21 days with bovine GH (via subcutaneously implanted osmotic minipumps) normalized RBC morphology and filterability. After withdrawal of GH, all parameters returned toward the presubstitutional levels. Neither cortisone nor thyroxine had any measurable effect on RBC morphology or deformability, indicating that GH deficiency contributes to the abnormal RBC morphology and rheology seen after hypophysectomy.

Animals↗

[Effect of hypophysectomy on gastrin release and antral gastrin concentration].

Hypophysectomy resulted in a lower amount of basal serum gastrin. In hypophysectomized rats, there was a release of serum gastrin after food intake; however, the serum gastrin level was lower 30 min postprandially. The most important effect of hypophysectomy is absence of repletion of antral gastrin after an initial postcibarial depletion. We conclude that the immediate synthesis of antral gastrin after food intake is inhibited by hypophysectomy.

Animals↗

Indications for hypophysectomy in diabetic retinopathy and cancer of the breast and prostate.

Hypophysectomy can be advised for diabetic patients whose vision is threatened by neovascular changes characterizing proliferative retinopathy. In the management of advancing breast cancer, hypophysectomy is recommended in postmenopausal (natural or induced) patients who have received two trials of hormonal therapy. We advocate wider application of hypophysectomy for advancing prostate cancer, where, when used in sequence after castration and administration of hormonal therapy, it will relieve pain and produce tumor regression in some patients unresponsive to other forms of treatment. Transsphenoidal cryohypophysectomy is a safe and effective means of pituitary ablation.

Breast Neoplasms↗

Monoamine oxidase and aspartate aminotransferase in cellular fractions of thyroid gland in rats after hypophysectomy and TSH stimulation.

UNLABELLED: Monoamine oxidase (MAO) and aspartate aminotransferase activities in cellular fractions of thyroid gland in rats after hypophysectomy and TSH treatment were investigated. MAO and aspartate aminotransferase activities in thyroid mitochondria were decreased after hypophysectomy and significantly increased after daily injection of TSH during five days to hypophysectomized rats. In microsomes after hypophysectomy a similar decrease of MAO activity was found but TSH was without effect on this activity. IN CONCLUSION: it is evident that MAO and aspartate aminotransferase in thyroid mitochondria the enzymes which could be a source for hydrogen peroxide to catalyze thyroid hormone synthesis are under the regulatory influence of TSH.

Animals↗

Effect of hypophysectomy and hormonal replacement on the uptake of Tc-99m methylene diphosphonate in the metaphysis and shaft of the rat femur: concise communication.

We have investigated the uptake of Tc-99m methylene diphosphonate (Tc-MDP) in the metaphysis and shaft of the rat femur as affected by hypophysectomy and hormonal replacement with growth hormone and thyroxine. Two hours following injection of Tc-MDP, the metaphysis and a specimen of shaft were obtained and the metaphysis-to-shaft radioactivity ratio was measured. By five days after hypophysectomy the metaphysis-to-shaft ratio fell from a control value of 3.8 +/- 0.2 (mean +/- s.e.) to 2.4 +/- 0.2 (p less than 0.05) and remained significantly decreased throughout the 30-day study. When daily hormonal replacement with 0.5 mg of bovine growth hormone and 10 micrograms of thyroxine (both administered intraperitoneally) was given, beginning on the eighth day after hypophysectomy, the metaphysis-to-shaft ratio of Tc-MDP returned to control levels in twelve days. This model demonstrates the effect of growth hormone and thyroxine on the distribution of Tc-MDP, and may be useful as a radiobioassay of net circulating skeletal growth-promoting activity.

Animals↗

The effects of hypophysectomy, thyroidectomy, and postoperative infusion of cortisol or adrenocorticotrophin on the structure of the ovine fetal lung.

We studied the effect of in utero hypophysectomy and replacement therapy with cortisol and adrenocorticotropin on maturation of lung structure in ovine fetuses. Twenty-two festuses underwent hypophysectomy in utero at 99-122 days of fetal gestation. At term (148-150 days), ten fetuses received an infusion of ACTH and six fetuses received an infusion of cortisol. The remaining fetuses were untreated. Morphometric analysis of the caudal lobe of the right fetal lung was performed and included measurement of minimum interalveolar wall thickness, numerical density of Type I and Type II pneumocytes in septal tissue, and volume density of septal tissue and air spaces in respiratory lung. The lung of the hypophysectomized animals differed from term controls in that alveolar walls were thicker, numerical density of Type I pneumocytes was less and that of Type II cells greater. Treatment with ACTH or cortisol caused lung structure to appear similar to the lungs of term control animals. We conclude that hypophysectomy impairs structural maturation and that structural maturation can be achieved by a relatively brief infusion of cortisol or ACTH at term.

Adrenocorticotropic Hormone↗