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Hypophysectomy or adrenalectomy of rats with insulin-dependent diabetes mellitus partially restores their responsiveness to growth hormone.

The studies reported herein were conducted to confirm that the pituitary gland is involved in maintaining growth hormone (GH) resistance in rats with insulin-dependent diabetes mellitus (IDDM) and to determine whether the adrenocorticotropic hormone (ACTH)-adrenal cortical axis is responsible. The rats were made diabetic by injecting streptozotocin (85 mg/kg body wt) IP once daily on two consecutive days. They were then injected with 15 IU insulin SC twice daily on two consecutive days to enable them to survive hypophysectomy or adrenalectomy. Intact nondiabetic (NonDb), diabetic (Db), hypophysectomized diabetic (HxDb), and adrenalectomized diabetic (AxDb) rats were injected twice daily with 50 micrograms porcine (p) GH or with 0.9% saline for 2 weeks following the surgeries. Serum glucose levels of the saline-injected Db, HxDb, and AxDb rats were significantly greater than those of the NonDb rats by 106%, 65% and 49%, respectively. However, the levels in the HxDb and AxDb animals were significantly lower than those of the Db group by 20% and 28%, respectively. Injections of pGH into NonDb rats increased serum glucose concentrations by 38%, over their saline-treated controls, and by 29% in AxDb rats. This diabetogenic effect of GH was not seen in any other group. Administration of pGH to Db rats failed to increase body weight gain, tall growth, tibial epiphysial plate width, or serum IGF-I concentration over saline-injected controls. By contrast, HxDb and AxDb rats injected with pGH showed significant increases in all four growth parameters. Total serum IGF-I concentrations in AxDb rats injected with pGH equaled those in NonDb controls. To determine whether the lack of corticosterone (B) in the AxDb rats was responsible for the reduced hyperglycemia and restored responsiveness to pGH, AxDb rats were given B in their drinking water at 5 or 25 micrograms/ml. Administration of B reduced the beneficial effects of adrenalectomy by restoring hyperglycemia and growth impairment, and partially restored resistance to the pGH injections. These studies confirm that the pituitary contributes to diabetic growth impairment and show that the ACTH-adrenal cortical axis is primarily responsible for the GH-resistant state that develops in rats with IDDM.

Adrenalectomy↗

Simplified hypophysectomy technique for young birds.

The present work introduces a modified oral approach to the pituitary gland of the immature bird with improved localization and visualization of the organ in situ. The hypophysectomy procedure is based on simplified instrumentation readily available or constructed with materials present in most, if not all, laboratories. The technique has the added advantage of minimal exsanguination, virtually no operative trauma, and allows for a rapid post operative animal recovery.

Animals↗

Gonadotropin-secreting pituitary tumor associated with hypersecretion of testosterone and hypogonadism after hypophysectomy.

OBJECTIVE: To review gonadotropin-secreting pituitary tumors and report the rare case of one of these tumors that caused high serum testosterone concentrations, followed by hypogonadism after hypophysectomy. METHODS: A case report is presented of a 61-year-old man who had decreased vision in his left eye, found by computed tomography of the sella to be attributable to a soft tissue pituitary mass with upward extension that caused elevation and deviation of the optic chiasm. Endocrine and pathologic evaluations are presented, and the treatment and follow-up course are discussed. RESULTS: Endocrine evaluation revealed a serum follicle-stimulating hormone (FSH) of 72.48 mIU/mL, luteinizing hormone (LH) of 31.65 mIU/mL, prolactin of 26.42 ng/mL, and total testosterone of 15.24 ng/mL (all values higher than the normal ranges). A soft tissue mass (3.2 by 2.5 by 1.2 cm) with negative immunocytochemical staining for prolactin and growth hormone but positive staining for synaptophysin, FSH, and LH was removed. One month postoperatively, the patient's chief complaints were a decrease in penile size and erectile dysfunction. Endocrine evaluation revealed a decreased LH of <0.3 mIU/mL, total testosterone of <0.2 ng/mL, and FSH of 4.3 mIU/mL. Three months later with testosterone replacement therapy, testosterone levels normalized, LH was <0.3 mIU/mL, and FSH was 3.9 mIU/mL. Thyroid function and adrenal function were normal before and after surgical intervention. CONCLUSION: This rare case indicates that gonadotropin tumors can produce a functional LH that can increase serum testosterone levels.

Follicle Stimulating Hormone↗

Effects of hypophysectomy and short- aing electron-microscopic study.

The follicular architecture of the thyroid gland of the rat following experimentally induced states of hypo- and hyperactivity was investigated by scanning electron microscopy and the findings correlated with both light and transmission electron-microscopic observations. By scanning electron microscopy, the microvilli on the apical surfaces of the follicular cells showed the most striking changes; following hypophysectomy, the cells were flattened and the microvilli had decreased in both size and number, whereas following propylthiouracil (PTU) administration the epithelial cells were enlarged, and marked hyperplasia and hypertrophy of the microvilli was present. Of particular interest is that the changes observed following PTU appeared to be identical in short- and long-term PTU-treated rats. Similarly, the heterogeneity of the follicular cells observed within the follicles was maintained under the various experimental conditions. Although the functional significance of these observations is not quite clear, it appears justifiable to assume that a reduction of luminal surface area of the follicular epithelial cell may hinder, whereas an increase may facilitate transport process across the apical cell membrane.

Animals↗

Pituitary and adrenal control of pancreatic endocrine function in the duck. II. Plasma free fatty acids, aminoacids, and insulin variations following hypophysectomy and replacement therapy with growth hormone and corticosterone.

The levels of plasma free fatty acids, aminoacids and insulin were studied in normal, hypophysectomized and beef growth hormone and/or corticosterone treated hypophysectomized ducks. Hypophysectomy decreased plasma free fatty acids, aminoacids and insulin levels; growth hormone and growth hormone + corticosterone treatments in hypophysectomized animals induced opposite changes, while corticosterone alone only increased the concentrations of plasma aminoacids and insulin. However, corticosterone enhanced the growth hormone effects on the three parameters. It is suggested that four feed-back mechanisms may be involved in the control of glucagon secretion by the anterior pituitary and the adrenal cortex : glucose-glucagon, free fatty acids-glucagon, aminoacids-glucagon and insulin-glucagon. In addition, in these experiments, insulin and glucagon always varied in opposite directions.

Amino Acids↗

[Cushing's disease successfully treated by transphenoidal hypophysectomy since eight years (author's transl) (proceedings)].

The authors show a case of true Cushing's disease by bilateral adrenal hyperplasia without pituitary tumor which is cured for eight years by only treated with transphenoidal hypophysectomy. They think that reaching by surgery, the nervous afferences from hypothalamus to hypophysis could play a part in ameliorating the pathologic relations which existed between two centers.

Adult↗

Effects of hypophysectomy, growth hormone, and thyroxine on protein turnover in heart.

Cardiac atrophy following hypophysectomy was accompanied by decreased heart content of RNA and polysomes and increased levels of ribosomal subunits, suggesting that protein synthesis was restricted by a reduced supply of ribosomes and an imbalance between rates of peptide-chain initiation and elongation. During perfusion in vitro, provision of palmitate restored the normal balance between rates of initiation and elongation but protein synthesis was lower in hearts of hypophysectomized than normal rats, reflecting the lower RNA content of hearts from hormone-deficient animals. After the period of atrophy had passed, or after treatment with growth hormone and thyroxine, heart RNA content and rates of protein synthesis were equal to or greater than those found in normal hearts. When plasma levels of amino acids, glucose, fatty acids, and insulin, and rates of beating and ventricular pressure development observed in normal and hypophysectomized rats were simulated during in vitro perfusion, hearts from hormone-deficient rats had reduced rates of protein synthesis but unaltered rates of degradation. Cathepsin D activity in heart homogenates (+ Triton X-100) was elevated during cardiac atrophy when expressed per g of tissue but not when expressed per heart.

Acetylglucosamine↗

[Proceedings: Prolactin adenoma revealed by gemellary? pregnancy after clomiphen therapy. Hypophysectomy during 5 th month of pregnancy (author's transl)].

A 25 year old woman had galactorrhea and secondary amenorrhea since her first pregnancy at 20 years. After several treatments with Clomiphene, menses reappeared for 2 months and she became pregnant. At admission, she was in her 4th pregnancy month and had headaches and bitemporal hemianopsia. Hypophysectomy was performed during 5th pregnancy month. Prolactin adenoma with hemorragic lesions was found. Parturition of normal twins occurred 8th month. Partial hypophyseal recovery took place for the following 2 years, but hyperprolactinemia reappeared too.

Adenoma↗

[The effect of insulin on amino acid accumulation and their incorporation into the proteins of incubated rat diaphragm. The effect of preliminary hypophysectomy and experimental diabetes].

A study was made of the effect of insulin on some indices of protein metabolism in the incubated muscle of the diaphragm obtained from intact rats, hypophysectomized animals, rats with alloxan diabetes and animals with a combined functional exclusion of the hypophysis and the pancreas. Preliminary hypophysectomy depressed and alloxan diabetes increased the effect of insulin on leucin-C14 incorporation into the protein of the diaphragm. At the same time both preliminary actions promoted an increase of sensitivity of the incubated diaphragm to insulin as seen in examination of accumulation of H3-alphaaminoisobutyric acid. Combined exclusion of the function of the hypophysis and the pancreas led to less pronounced changes in the sensitivity of the diaphragm to insulin than each of the actions separately.

Amino Acids↗

[Endoscopic transnasal sphenoidal approach in hypophysectomy].

OBJECTIVE: To report the anesthetization and surgical method of transnasal-sphenoidal endoscopic approach in hypophysectomy. METHODS: Forty-two cases with pituitary tumor underwent tranasal-sphenoidal endoscopic surgery and 37 out of 42 accepted local anesthesia and sedation. RESULTS: No complications had occurred, the operations went successfully with less blood loss. Postoperative endoscopic follow-up period was performed at 6 to 35 months. The symptoms were improved in all patients. CONCLUSION: Our results show that transnasal-sphenoidal endoscopic approach under local anesthesia in the treatment of pituitary tumor seems to be a safe simple and valuable way.

Adolescent↗

Electrorhinomanometric evaluation of nasal functions in transseptal-transsphenoidal hypophysectomy.

OBJECTIVE: The prospective study in 23 patients, who were undergone transseptal-transsphenoidal hypophysectomy, underlines the rhinologic aspects of this technique. MATERIALS AND METHODS: Preoperative and postoperative subjective complaints were compared, postoperative nasal respiratory functions were evaluated by means of electrohinomanometry. RESULTS: Nasal respiratory functions were preserved postoperatively in the patients with normal preoperative nasal anatomy (no statistical difference); while, in patients with obstructive deviation of the nasal septum, an improvement in nasal respiratory functions were noted as a result of simultaneously performed septoplasty (p < 0.01). CONCLUSION: Our results emphasize the importance of the collaboration of otorhinolaryngology and neurosurgery teams for the sake of postoperative nasal functions.

Adult↗

Some hormonal factors (hypophysectomy, castration and testosterone administration) modifying the course of "compensatory" muscle hypertrophy in the rat.

1. Maximum compensatory hypertrophy of the soleus and plantaris muscle in male rats is attained seven days after tenotomy of the gastrocnemius muscle (39% and 9% respectively). When tenotomy of the gastrocnemius was performed seven days ater hypophysectomy, hypertrophy in these two muscles was aproximately half that found in control animals. 2. After 81-day castration of young male rats the weight of the saleus and plantaris was reduced and hypertrophy following tenotomy of the gastrocneumius muscle did not develop. 3. Chronically castrated rats received testosterone two weeks prior to tenotomy of the gastrocnemius and a week during the muscle hypertrophy phase. Hypertrophy of the soleus in castrated rats which had received testosterone seven days after tenotomy of the gastrocnemius was 25% as compared with muscles of castrated animals. The corresponding value in the plantaris muscle was 10%. 4. These results indicate that even calf muscles of the rat, namely the soleus and plantaris muscles, are significantly affected by testosterone under these conditions, although it is not, as yet, clear whether its action is direct or indirect.

Animals↗

Technical note: removal of the unfragmented pituitary gland (hypophysectomy) in the rat.

A technique to excise the pituitary gland (hypophysis) in rats is described. The basisphenoid bone is reached from the ventral neck and is perforated to expose the pituitary gland and its stalk. An aspirator allows the removal of the hypophysis and the stalk, including pars tuberalis, in one piece. The advantages of this new technique include: 1) immediate verification of the entirety of hypophysectomy; 2) broad operating field which exposes the pituitary stalk up to the hypothalamus; 3) the use of tracheal intubation and artificial respiration to improve postoperative recovery and to allow expanded operation field even during prolonged surgery. Pre- and postoperative care are described. The mean survival rate after this type of operation was 79% in rats weighing 50 to 130 g and 90% in rats larger than 130 g.

Animals↗

External rhinoplasty approach to transsphenoidal hypophysectomy.

The external rhinoplasty approach is a modification of the well recognized transseptal transsphenoidal hypophysectomy technique first introduced by Cushing in 1910. Our approach has been used successfully in 75 cases over a six year period, demonstrating its efficacy and safety. It provides a simple, reliable, rapid technique for exposing the septum and the floor of the nose with excellent exposure to the sphenoid sinus and pituitary gland. There has been no loss of nasal tip projection or other cosmetic deformity.

Adolescent↗

Effects of hypophysectomy and alterations in spermatogenic function on Leydig cell volume, number, and proliferation in adult rats.

The two major objectives of this study were to determine (i) whether the pituitary is required to maintain Leydig cell number per testis, and (ii) whether alterations in spermatogenic function in the absence of LH can affect Leydig cell volume, number, and 3H-thymidine incorporation in vivo. Four experimental treatments tested the combinations of two factors: (i) the intact pituitary vs hypophysectomy (Hypox); and (ii) arrested vs active spermatogenesis. Subdermal Silastic capsules were used to deliver a low dosage of estradiol in addition to a low dosage of testosterone (TE), which arrested spermatogenesis, or a high dosage of testosterone (HTE) which maintained active spermatogenesis. All four treatments (TE, HTE, Hypox and Hypox-HTE) inhibited LH secretion for 16 weeks. Control rats were sham hypophysectomized. Leydig cell volume per testis and the volume of an average Leydig cell decreased 70-85% (P less than 0.01 vs controls) in all treated rats, whether deprived of LH (TE) or of all pituitary secretions (Hypox), and whether spermatogenesis was arrested (TE, Hypox) or maintained by exogenous testosterone (HTE, Hypox-HTE). This result suggested that LH was the only factor required to maintain Leydig cell volume, since the absence of other pituitary factors or alterations in spermatogenic function could not override or modify the effect of LH deprivation. No significant differences were found in Leydig cell number per testis or the proportion of Leydig cells labeled with 3H-thymidine among control and experimentally treated rats. In contrast to Leydig cell volume, which depended on LH, Leydig cell number and Leydig cell division were maintained at control values in the absence of pituitary factors and spermatogenic function for 16 weeks.

3-Hydroxysteroid Dehydrogenases↗

[Effect of hypophysectomy, hypophyseal explants and ACTH on the growth of human melanomas in diffusion chambers].

Under study was the hypophysis influence on the growth of human melanoma explants, cultivated in the abdominal cavity of mice and rats. The heterotransplants growth was compared in intact and hypophysectomized animals exposed to ACTH, and also the effect of the murine hypophysis explanted into the adjacent chamber compartments on the melanoma explants growth was investigated. The growth was assessed by a square area of the explants growth zones. ACTH and the hypophysis explanted were found to render a stimulating effect on the growth of tumor heterotransplants. Hypophysectomy in rats would suppress the growth of all melanoma explants under investigation. When injecting ACTH into hypophysectomized animals the growth of melanoma heterotransplants in the chambers does not differ from that in control series.

Adrenocorticotropic Hormone↗

Effects of combined hypophysectomy and cyproterone acetate on the adrenal chromaffin cells of the rat. Evidence for postnatal migration of adrenal chromaffin cells.

A light and electron-microscopic study was performed concerning the effects of hypophysectomy (HP) followed by cyproterone acetate (CA) treatment on the adrenal chromaffin cells of the rat. The latter drug is reported to interfere with steroid biosynthesis. When given following HP, CA was found to induce degeneration in the inner cells of the zona fasciculata and a marked fall in the blood corticosterone level. The adrenal chromaffin cells which were depleted after the administration of reserpine at the beginning of the experiment failed to recover two weeks later. In addition, some of the depleted chromaffin cells migrated towards the outer cells of the zona fasciculata, had the appearance of pheochromoblasts and showed features of increased synthetic activity. The results are discussed in the light of the generally accepted functional relationship between the cells of the adrenal cortex and the medulla and following a marked fall in the concentration of blood corticosterone, a chemobiotaxis is suggested between the chromaffin and adrenal cortical cells.

Adrenal Cortex↗