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Effects of hypophysectomy and growth hormone treatment on renal hydroxylation of 25-hydroxycholecalciferol in rats.

Growth hormone stimulates intestinal calcium absorption. This action has been linked to vitamin D metabolism. We have investigated the effects of hypophysectomy and GH treatment on renal metabolism of 25-hydroxycholecalciferol (25-OH-D3). Renal hydroxylation of 25-OH-D3 was measured in vitro using the renal slice technique. Experiments were performed in young F344 rats fed a vitamin D-replete, low calcium diet for 4 weeks. In hypophysectomized rats, renal conversion of 25-OH-D3 to 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) was markedly reduced compared with sham-operated rats. Renal conversion of 25-OH-D3 to 24,25-(OH)2D3 was markedly increased in hypophysectomized rats compared with sham-operated rats. Treatment of hypophysectomized rats with rat GH (rGH) for 10 days resulted in a significant increase in renal conversion of 25-OH-D3 to 1,25-(OH)2D3 and a significant decrease in conversion to 24,25-(OH)2D3. Rat GH treatment caused no significant changes in serum levels of immunoreactive parathyroid hormone. Serum calcium concentrations were similar in all groups, and serum phosphorus was low in hypophysectomized rats. Treatment of hypophysectomized rats with ovine GH for 6 days caused changes which were much less pronounced than those induced by rGH. Renal conversion of 25-OH-D3 to 1,25-(OH)2D3 and 24,25-(OH)2D3 correlated well with growth rate (weight gain). These results suggest that GH, either directly or indirectly, modulates renal metabolism of 25-OH-D3.

24,25-Dihydroxyvitamin D 3↗

Effects of hypophysectomy and subsequent FSH and testosterone treatment on inhibin production by adult rat testes.

The hormonal control of inhibin production by adult rat testes was investigated using an in-vitro inhibin bioassay validated for the measurement of inhibin activity in charcoal-treated rat testicular extracts. The effect of hypophysectomy examined at 16 h, 3, 7 and 42 days after surgery showed a decrease in testicular inhibin content and seminiferous tubule fluid production by 7 days and a decrease in inhibin production by 42 days. Serum FSH and LH were suppressed 3 days after surgery. In 30-day chronically hypophysectomized adult rats treated for 3 days with twice daily s.c. injections of (a) human FSH (hFSH, 22 i.u./rat per day), (b) testosterone (5 mg/rat per day), (c) hFSH + testosterone (same doses as a and b), or (d) human chorionic gonadotrophin (hCG, 12 i.u./rat per day), hFSH or hFSH and testosterone stimulated an increase in testicular inhibin content but not in inhibin production or tubule fluid production. Testosterone and hCG had no effect on these parameters. It is concluded that in vivo, FSH alone stimulates an increase in testicular inhibin content. The failure to observe an increase in inhibin production in vivo is attributed to the suppression of seminiferous tubule fluid production under the same experimental conditions.

Animals↗

Effects of hypophysectomy and growth hormone infusion on rat hepatic carbonic anhydrases.

Rat liver exhibits a reversed sexual dimorphism of its two endogenous soluble carbonic anhydrase (CA) isozymes, CA II and CA III. Normal males have hepatic CA III concentrations ten-twenty times those in the female, while female liver contains two-three times more CA II than the male. Hypophysectomy abolishes this sexual differentiation, having no effect on male liver but producing isozyme concentrations in the female liver similar to those in the male. Infusion of a continuous level of GH into male rats induces a female-like isozyme pattern for both CA II and CA III.

Animals↗

Effect of hypophysectomy and acute administration of growth hormone (GH) on GH-receptor binding in chick liver membranes.

The effects of hypophysectomy on GH binding to liver membranes of young chicks were studied 3 days and 1 week after surgery. Specific binding of 125I-labelled chicken GH (cGH) to MgCl2-treated liver microsomal fractions of hypophysectomized animals was two- to fivefold greater than to those of sham-operated or control (non-operated) birds. This effect was due to a rise in binding capacity rather than a change in binding affinity of the GH receptor. Two daily injections of cGH (20 micrograms/animal) returned the number of hepatic GH receptors from hypophysectomized chicks to the level of the sham-operated ones. Administration of GH to the latter group did not cause a significant lowering of specific binding or number of receptors. No positive correlation between GH binding and plasma concentrations of insulin-like growth factor-I (IGF-I) was observed; although GH binding increased, IGF-I levels were lower for the hypophysectomized group. Since the number of hepatic GH receptors and the plasma GH levels were inversely correlated, it was concluded that the GH receptors in the liver of the chicken can be down-regulated by GH. This possibly explains why GH binding is low in posthatch and young chicks, because circulating GH concentrations are high during this period.

Animals↗

Hypothalamic release of atrial natriuretic factor and beta-endorphin into rat hypophysial portal plasma: relationship to oestrous cycle and effects of hypophysectomy.

The release of beta-endorphin and atrial natriuretic factor (ANF) into hypophysial portal plasma was investigated in male and female Wistar rats. The principal aim of the study was to investigate the possible role of beta-endorphin and ANF in the hypothalamic control of LH and prolactin secretion. In male rats, anaesthetized with urethane, the concentrations of beta-endorphin in portal blood collected immediately after hypophysectomy were within the same range as those in peripheral plasma. Furthermore, electrical stimulation of the median eminence did not increase the portal plasma concentrations of beta-endorphin. In female rats, anaesthetized with alphaxalone, the portal plasma concentrations in long-term (6-8 weeks) or acutely hypophysectomized rats were significantly greater than those in peripheral plasma. In acutely hypophysectomized female rats the concentrations and contents of beta-endorphin in portal plasma collected at 10.00-11.30 h of pro-oestrus were significantly (approximately sixfold) greater than at dioestrus or at 20.00-21.00 h of pro-oestrus, but these changes were not consistently seen in all experiments. In female rats in which the pituitary gland was not removed for portal blood collection, portal plasma contents of ANF remained unchanged throughout the day of pro-oestrus, suggesting that it is unlikely that ANF is involved in the spontaneous LH or prolactin surge. The effects of ovarian steroids on the secretion of hypothalamic ANF and beta-endorphin were determined by measuring the portal plasma concentration of ANF and beta-endorphin on the morning of presumptive pro-oestrus in rats ovariectomized 24 h previously and injected with either oil or oestradial benzoate (OB). Portal plasma contents of ANF were significantly lower in OB- compared with oil-treated rats, suggesting that oestradiol inhibits ANF release into rat hypophysial portal plasma. In contrast, there were no significant between-group differences in the content or concentration of beta-endorphin in portal plasma. Thus, the increased beta-endorphin in the portal plasma of some of the intact animals during the morning of pro-oestrus is not due to the preovulatory surge of oestradiol-17 beta. The output of beta-endorphin into portal blood in long-term hypophysectomized rats was lower than in dioestrous or pro-oestrous rats in which the pituitary gland was removed immediately before portal blood collection.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The effect of fetal hypophysectomy with or without ACTH replacement on the molecular weight profile of enkephalin-containing peptides in the adrenal medulla of the fetal sheep.

We have investigated the possible role of the fetal pituitary and ACTH in the control of the synthesis and post-translational processing of the enkephalin precursor, proenkephalin A (proEnk A), in the fetal sheep adrenal gland in late gestation. Fetal hypophysectomy (n = 8) or sham operations (n = 4) were performed between 109 and 118 days of gestation. At 138-139 days, either ACTH(1-24) (10.5 micrograms/0.24 ml saline per h, n = 4) was infused intravenously for 72 h into hypophysectomized fetal sheep or 0.9% (w/v) NaCl alone (0.24 ml/h, n = 4) was infused for 72 h into hypophysectomized fetal sheep and sham-operated animals. At the end of the infusion the pregnant ewe was killed and left or right adrenal glands (n = 12) were collected from the fetal sheep that were intact and given saline (Intact + sal; n = 4), hypophysectomized and given saline (Hx + sal; n = 4) and hypophysectomized and given ACTH (Hx + ACTH; n = 4). Each adrenal was homogenized in acid (acetic acid (1 mol/l)/HCl (20 mmol/l)/2-mercaptoethanol (0.2%)). After centrifugation, the supernatant was loaded onto a Sephadex G-75 column (2.0 x 50 cm), eluted at 80 ml/24 h and fractions were collected (5 ml, n = 42). An aliquot of each fraction (2 ml) was dried down prior to enzymatic digestion (trypsin/carboxypeptidase B) and oxidation with H2O2, and assay for methionine-O-enkephalin (immunoreactive Met-O-Enk).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗

Regulation of gill prolactin receptors in tilapia (Oreochromis niloticus) after a change in salinity or hypophysectomy.

Prolactin (PRL) receptors in gill tissue have been analyzed in tilapia (Oreochromis niloticus) after transfer from fresh water (FW) to brackish water (BW). This study has indicated the presence of only one class of tilapia PRL (tiPRL) receptor whatever the salinity. After transfer, however, the percentage of specific binding of the two forms of tiPRL (tiPRLI and tiPRLII) increased significantly. Scatchard analysis of tiPRLI binding indicated an increase in receptor affinity, an effect which was not accompanied by any change in receptor specificity. Transfer to BW also caused the number of tiPRL receptors to increase rapidly, remaining high in fish adapted to BW for 28 days. Based on the sharp reduction in plasma tiPRLI and tiPRLII levels after transfer to BW, one possible explanation may be that tiPRL itself is an important factor regulating the number of free receptors. This hypothesis finds support in the fact that the number of tiPRL receptors also increased in hypophysectomized fish reared in FW. However, the absence of change in receptor affinity after hypophysectomy suggested that yet other factors are involved in tiPRL receptor regulation during the transfer from FW to BW. The paradoxically high numbers of tiPRL receptors in the gills of BW-adapted tilapia, even though PRL is known to be a FW-adapting hormone, is discussed with regard to the environment in which tilapia live.

Animals↗

The effects of hypophysectomy upon DNA synthesis in rat oral epithelium.

Ten hypophysectomized and 10 normal female albino rats, 50-days-old, were kept for 5 days and treated with tritiated thymidine 1 hour before sacrifice of the animals. The animals were weighed and the histomorphology of the palate epithelium was studied including the thickness, cell density, and DNA labeling index. The hypophysectomized rats failed to gain weight after 5 days. The palatal epithelium showed a normal morphology indicating the hypophysectomy allowed for differentiation of squamous epithelium. There was a significant reduction in the thickness of the epithelium and a reduced cell density. This was attributed to a significant decrease in DNA synthesis. The epithelial cells were lost from the surface without adequate replacement due to an expected depression in mitotic activity. DNA synthesis may be depressed due to reduced ATP synthesis resulting from suboptimal glucose metabolism and depression in protein synthesis.

Amino Acids↗

An autopsy case of adrenal insufficiency 20 years after hypophysectomy: relation between stress and cause of death.

A 63-years-old man was found dead with the body soaking in water lying face up on a riverbank. Autopsy and diatom examination demonstrated that the cause of death was drowning. He had undergone hypophysectomy 20 years earlier. Autopsy, pathological and endocrinological findings demonstrated secondary and chronic hypothyroidism, hypogonadism, and adrenal insufficiency. The cadaver had fallen into the river, and received numerous wounds such as abrasions and subcutaneous hemorrhage. Moreover, it was suspected that he had developed hypothermia before death. Cortisol in the blood and 17- OHCS in urine were within the reference range. We suspect that the adrenocortical hormone was secreted into the blood as a result of various stresses due to wounds and hypothermia. However, it was suspected that sufficient hormone might not be secreted due to chronic adrenal insufficiency. This insufficient cortisol causes the decrease in the stress resistance, and might influence his cause of death. Moreover, as hypothyroidism decreases thermogenesis, he might have fallen into hypothermia easily. In addition, because both adrenocortical insufficiency and hypothyroidism caused the hypoglycemia, he might have fallen into the loss of consciousness. Therefore, it was considered that he had died by drowning, in relation to the adrenocortical insufficiency and panhypopituitarism.

Adrenal Insufficiency↗

The radiology of transsphenoidal hypophysectomy: a review of 100 cases.

This report describing the radiology of transsphenoidal hypophysectomy based on a review of 100 consecutive surgical procedures. Preoperative laminographic evaluation of the sphenoid sinus is an important aid in planning the most direct surgical approach to the pituitary. It is also useful in defining the many anatomic structures that may be injured inadvertently at the time of surgery. Intraoperative radiography or fluoroscopy is helpful in identifying the sella floor and as an aid in preventing loss of orientation within a capacious sinus. Various changes occur within the sphenoid sinus following surgery, some transient and others persistent. The surgical defect is usually difficult to identify on routine roentgenograms but is clearly visible on lateral laminography. A persistent soft tissue mass within the sinus is usually a manifestation of fascia and fat placed as a seal within the sinus.

Humans↗

Effects of hypophysectomy and testosterone treatment on the urinary excretion of zenarestat in rats.

1. The effects of hypophysectomy and androgen treatment on the urinary excretion of zenarestat were investigated in Sprague-Dawley rats. 2. Hypophysectomized male rats and normal female rats has similar urinary excretion of zenarestat which was much greater than that of normal male rats. 3. Treatment of male and female hypophysectomized rats with testosterone resulted in the urinary excretion of zenarestat characteristic of intact adult male rats. 4. Urinary secretion of zenarestat in rats is independent of pituitary hormone and is suppressed only by androgen.

Animals↗

Effect of hypophysectomy and hormone replacement on fatty elongation in isolated microsomes of rat testes.

Effect of hypophysectomy on fatty acid elongation was investigated in isolated rat testicular microsomes incubated with [14C]malonyl CoA. Hypophystectomy resulted in a 40% decrease in total incorporation of 14C into fatty acids of microsomes. Several 18- and 20-carbon fatty acids of testicular microsomes from hypophysectomized rats had less 14C than did those from nonhypophysectomized ones, whereas only docosa-7,10,13,16-tetraenoic acid (22:4w6) had more 14C. Testosterone injected subcutaneously into hypophysectomized rats at a dose of 0.5 mg per day for eight days posthypophysectomy had no apparent effect on either the total 14C incorporated or the distribution of the 14C in the various fatty acids. Daily subcutaneous injections of 50 or 100 micrograms follicle stimulating hormone (FSH) had some effect on both total incorporation and distribution of 14C. Addition of 0.5 mg testosterone to the 50 micrograms FSH gave the same results as the FSH alone. Smaller amounts of stearic acid (18:0) and linoleic acid (18:2) and increased amounts of docosa-4,7,10,13,16-pentaenoic acid (22:5w6) were present in the microsomes of hypophysectomized compared to nonhypophysectomized rats. Testosterone replacement did not affect these differences, but FSH administration was partially effective in altering the values toward those observed in nonhypophysectomized rats. Results obtained in these experiments indicate that there is inhibition of the testicular microsomal fatty acid elongation system in hypophysectomized rats and that, although testosterone is not at all effective in relieving the inhibition, FSH administration is at least partly effective.

Animals↗

Carotico-cavernous fistula after trans-sphenoidal hypophysectomy.

A case is presented of a 48-year-old woman with an iatrogenic carotico-cavernous fistula consequent upon a transphenoidal hypophysectomy. Successful closure of the fistula was achieved by interventional radiology. The causes and management of vascular injuries during trans-sphenoidal pituitary surgery are reviewed and discussed.

Arteriovenous Fistula↗

Balloon catheter occlusion for cavernous carotid artery injury during transsphenoidal hypophysectomy. Case report.

During transsphenoidal hypophysectomy for pituitary ablation in a patient with disseminated breast cancer, brisk arterial hemorrhage occurred during separation of adhesions between the pituitary gland and the wall of the cavernous sinus. Hemorrhage was controlled by placement of a Prolo balloon catheter into the internal carotid artery (ICA) that occluded the site of hemorrhage. The patient experienced no neurological sequelae. The cervical ICA was easily exposed for insertion of this double-lumen catheter. With the image intensifier already in position, injection of contrast material through the arteriography lumen allowed precise localization of the site of injury and directed positioning of the balloon for control of the hemorrhage.

Carotid Artery Injuries↗

Lysosomal enzymes in the rat harderian gland are altered by either bromocriptine treatment or hypophysectomy and hormone replacement therapy.

Four groups of adult male hypophysectomized rats were injected subcutaneously twice daily between 0800-0900 hr and 1600-1700 hr with either saline diluent, 150 micrograms sheep prolactin and/or growth hormone (GH); intact rats received either saline or 150 micrograms bromocriptine twice daily. After 4 days of treatment, lysosomal enzyme assays revealed significant elevations in both acid phosphatase and alpha-mannosidase enzyme activities in the Harderian glands of saline-injected hypophysectomized rats compared to those in intact controls. beta-Glucuronidase levels were depressed and hexosaminidase activity unaffected by hypophysectomy treatment alone compared to intact controls. Lysosomal enzyme activities in hypophysectomized animals treated with prolactin were not different from the hypophysectomized control animals. However, treatment with GH alone or in combination with prolactin had a significant inhibitory effect on beta-glucuronidase, hexosaminidase, and alpha-mannosidase enzyme activities in the Harderian gland of hypophysectomized animals. Bromocriptine treatment in intact rats only elevated acid phosphatase activity. In summary, the patterns of responses did not reveal a role for prolactin in the control of Harderian gland lysosomal enzyme activities by the pituitary. However, some of the influence on this target system may be exerted by growth hormone.

Acid Phosphatase↗

Effects of hypophysectomy and the insulin-like and anti-insulin pituitary peptides on carbohydrate metabolism in yellow Avy/A (BALB/c x VY)F1 hybrid mice.

The amino-terminal portion of human growth hormone, residues 1-43 (hGH1-43), has insulin-potentiating action, while a hyperglycemic pituitary peptide (HP), which co-purifies with human growth hormone (hGH), is antagonistic to the action of insulin. The effects of hGH, hGH1-43, and HP on glucose metabolism were assessed in young (4-5 weeks) and adult (6-8 months) hypophysectomized yellow Avy/A mice which lacked any interfering endogenous pituitary hormones, and compared with age-matched intact obese yellow Avy/A and lean agouti A/a mice. Treatment with hGH1-43 or HP did not promote body growth in hypophysectomized yellow mice; but after 2 weeks of treatment with hGH, there was a significant increase in body weight (P less than 0.05). Treatment with HP raised blood glucose and lowered insulin concentrations in obese yellow mice, but not in agouti or hypophysectomized yellow mice. The severely impaired glucose tolerance of the hypophysectomized yellow mice was improved by acute (60 min) and chronic (3 days) treatment with hGH1-43 as well as by 2 weeks of treatment with hGH; in contrast, HP had no effect. Glucose oxidation in adipose tissue from obese yellow mice was low and showed essentially no response to stimulation by insulin at doses lower than 1000 microunits/ml. Basal glucose oxidation rates in adipose tissue taken from agouti and hypophysectomized yellow mice were significantly higher (P less than 0.001) than those in tissue from obese yellow mice, and the rates responded significantly (P less than 0.05) to 100 microunits/ml insulin. The insulin binding affinities in liver membranes from agouti mice were higher than those from either obese or hypophysectomized yellow mice. The insulin receptor densities were similar in both agouti and obese yellow mice, but higher in hypophysectomized yellow mice (P less than 0.05). Treatment with hGH1-43 slightly increased, although not significantly, the insulin receptor density in yellow obese mice while hGH showed essentially no change. Therefore, hypophysectomy appeared to increase tissue response and decrease insulin resistance by increasing receptor numbers and lowering the circulating insulin levels. Furthermore, the insulin-like action of hGH was elicited directly in vivo by hGH1-43 in hypophysectomized yellow mice.

Adipose Tissue↗