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Hypophysectomy-induced regression of female rat lacrimal glands: partial restoration and maintenance by dihydrotestosterone and prolactin.

PURPOSE: Previous studies have implicated androgens and one or more as yet unknown pituitary or pituitary-dependent factors in the regulation of certain lacrimal gland functions. Many observations suggest that prolactin (PRL) might well be one of these factors. This study was designed to determine the effect of hypophysectomy on biochemical markers of exorbital lacrimal gland secretory capacity and to determine the extent to which dihydrotestosterone (DHT) and prolactin reverse these changes. METHODS: Female rats were hypophysectomized and, 5 days later, were treated for 2 days with DHT (0.25 or 1 mg/kg), PRL (1 or 5 mg/kg), combinations of the low or high doses of DHT and PRL, or vehicle only. The animals were killed, and crude membrane fractions were isolated from their lacrimal glands. An untreated group served as control. RESULTS: Lacrimal glands atrophied rapidly after hypophysectomy, losing 40% of their total and membrane-associated protein and 50% of their total DNA within 5 days. Total Na+,K(+)-ATPase and acid phosphatase activities and beta-adrenergic receptor number were decreased by half, whereas alkaline phosphatase activity and muscarinic cholinergic receptor number were reduced by 25% to 30%. DHT treatment increased total DNA above control values; it partially restored the amount of protein in the gland, the Na+,K(+)-ATPase and acid phosphatase activities, and the beta-adrenergic receptor number; and it fully restored the alkaline phosphatase activity. Prolactin treatment partially restored the amount of protein in the gland and the Na+,K(+)-ATPase activity; it fully restored the alkaline phosphatase activity and cholinergic receptor number; but it had no effect on the acid phosphatase activity or the beta-adrenergic receptor number. The high dose of DHT reduced the increase in cholinergic receptor number elicited by PRL. The high dose of PRL reduced the increases of total Na+,K(+)-ATPase and acid phosphatase elicited by DHT. CONCLUSIONS: These findings suggest that DHT and PRL exert general trophic actions on the lacrimal gland and specifically on lacrimal Na+,K(+)-ATPase, acid phosphatase, and neurotransmitter receptors. They also suggest that excessive levels of either hormone may be deleterious to secretory function. Because sex hormone levels are prone to wide fluctuations in women, our results also suggest a plausible hypothesis to account for the greater incidence in women of lacrimal insufficiency.

Acid Phosphatase↗

Entactin ultrastructural immunolocalization in the basal laminae of mouse seminiferous tubules and with only subtle changes following hypophysectomy.

While entactin has been recently reported in the mouse seminiferous tubule lamina propria at the light microscope level, the purpose of this paper was twofold: 1) to determine the ultrastructural localization of entactin with the two basal laminae that form the lamina propria of the mouse, and 2) to determine if immunoreactive entactin changes following hypophysectomy. The localization of entactin was demonstrated by three different means: 1) immunofluorescent localization in semi-thin cryosections of the testis, 2) immunoperoxidase staining in a preparation of isolated lamina propria, and 3) immuno-gold staining in ultra-thin sections of testis. These techniques all demonstrated that immunoreactive entactin is present in both the inner and outer basal laminae of the mouse seminiferous tubules and is co-localized with laminin. These results are consistent with previous work that demonstrated entactin is synthesized and secreted by both Sertoli and peritubular myoid cells. Because both Sertoli cells and peritubular myoid cells are androgen-responsive cells, we wanted to determine if hypophysectomy alters the testicular distribution of entactin. Changes in immunoreactive entactin and laminin in the basal laminae were observed in semi-thin cryosections of the testes from hypophysectomized mice up to 6 weeks after surgery. The results demonstrated that during this time period, while most of the spermatogenic cells degenerated, the intensity of immunoreactive entactin and laminin remained nearly unchanged, as the seminiferous tubule basal laminae took on an increasingly wavy appearance. This suggests that the relative concentration of entactin and laminin in the basal lamina is stable, and not dependent on the presence of normal spermatogenesis and pituitary hormones.

Animals↗

Experience with sublabial transseptal transsphenoidal hypophysectomy at the Universiti Kebangsaan Malaysia.

The transseptal transsphenoidal hypophysectomy has become a relatively frequent procedure in recent years. We performed 20 such procedures between January 1984 and December 1987 for various pituitary disorders. Significant complications such as CSF rhinorrhea, meningitis, diabetes insipidus, haemorrhage and septal perforation are discussed. The mortality rate for the series was 5%. In analysing the data, we feel that this technique of hypophysectomy is a safe procedure.

Adolescent↗

Synthesis and secretion of rat albumin in vivo, in perfused liver, and in isolated hepatocytes. Effects of hypophysectomy and growth hormone treatment.

The effects of hypophysectomy on albumin and total protein synthesis in rat liver were investigated in vivo, in perfused liver, and in isolated hepatocytes. In all systems, hypophysectomy resulted in about a 50% decrease in the rate of total protein synthesis and a 30 to 50% decrease in the relative rate of albumin synthesis. Albumin synthesis accounted for 11 to 13% of total protein synthesis in all normal systems, but represented only 5 to 8% of the total in all systems derived from hypophysectomized rats. Growth hormone, administered subcutaneously to hypophysectomized rats for 5 days, restored the relative rate of albumin synthesis to normal in vivo; however, only partial restoration was demonstrated in the in vitro systems. Perfused livers and isolated hepatocytes exhibited linear rates of total protein and albumin secretion for 3 h. The rate of albumin secretion by normal perfused livers was 3 times that of perfused livers from hypophysectomized animals, being 0.54 and 0.17 mg/g of liver/h, respectively. Isolated hepatocytes synthesized total protein and albumin at nearly the same rate as perfused livers. The amount of albumin secreted by cells derived from normal and hypophysectomized rats was 0.38 and 0.10 mg/ml of packed cells/h, respectively. Ribosome half-transit times for albumin and total liver protein were 1.6 to 1.7 min in isolated liver cells derived from both normal and hypophysectomized rats. Analysis by polyacrylamide gel electrophoresis showed no difference in the qualitative distribution of the proteins secreted by perfused livers and isolated hepatocytes.

Albumins↗

The treatment of Cushing's disease by trans-sphenoidal hypophysectomy.

Thirteen patients aged 24 to 65 with Cushing's disease have been treated by transphenoidal hypophysectomy. There was one incident of meningitis and one late death from myocarditis. No radiotherapy was given. In 12 patients pituitary histology showed Crooke's changes and an adenoma was present in seven. On review of the 12 survivors two to 11 years later, 11 are in complete remission. One patient still showed some clinical features of Cushing's syndrome but steroid levels were normal. In five of the seven premenopausal women normal menstruation has returned and pregnancy has occurred in three. In four patients replacement hormone therapy is no longer required and a further four take only partial treatment. We conclude that transphenoidal hypophysectomy is an effective treatment for Cushing's disease.

Adrenal Cortex Function Tests↗

Maintenance of obesity following hypophysectomy in the obese-hyperglycemic mouse (ob/ob).

In order to examine the role of the pituitary in the obese-hyperglycemic syndrome, obese (ob/ob) and nonobese sibling (OB/?) mice were sham-operated or hypophysectomized by a parapharyngeal method at 60 to 90 days of age and subsequently weighed for nine weeks. Completeness of hypophysectomy was assessed by microscopic examination of stained serial sections of the brain and attached hypophyseal capsule. Complete hypophysectomy resulted in a moderate weight loss in the obese mice and attenuated further increases in adiposity, but it failed to eliminate the adiposity already established prior to surgery as determined from Lee index values. We tentatively conclude that neither the pituitary nor the target organs it controls represent the site of the primary genetic abnormality that maintains the obesity of the ob/ob.

Animals↗

Modulation of lipids in the chick liver by "hypophysectomy" and replacement.

The effect of "hypophysectomy" by means of surgical decapitation upon total lipids in developing chick embryo liver has been studied from 10.5 to 18.5 days of incubation. "Hypophysectomy" results in subnormal levels of hepatic lipid per whole liver throughout this period. Data expressed as mg lipid per 100 mg liver corrected wet weight also results in decreased liver lipid concentrations after day 14.5. In "hypophysectomized" embryos bearing pituitary transplants, liver total lipid amounts and concentrations are significantly increased toward normal values. The possible role(s) of the pituitary in the control of embryonic liver lipid metabolism is discussed.

Animals↗

Disturbed hypothalamic blood flow autoregulation in the rat following hypophysectomy: a role of pituitary beta-endorphin?

The effect of hypophysectomy on hypothalamic blood flow autoregulation was studied in anesthetized, artificially ventilated rats. Local hypothalamic blood flow (HBF, H2-gas clearance method) was measured. Efficiency of autoregulation was tested by determining HBF during standardized hemorrhagic hypotension when systemic arterial pressure was lowered to 80, 60 and 40 mm Hg by consecutive, step-wise bleeding. HBF autoregulation was well maintained until 80 mmHg, but not completely at 60 and 40 mmHg arterial pressure in the sham-operated control group. In contrast, autoregulation was abolished at all levels in the hypophysectomized rats: HBF followed the changes in arterial pressure in these animals. Following hypophysectomy, the concentration of immunoreactive beta-endorphin (beta-EP) decreased drastically in plasma but remained unchanged in cerebrospinal fluid. Administration of beta-EP (200 pg/100 g b. wt.) to hypophysectomized rats by the intravenous route had no effect on autoregulation, while intracerebroventricular administration of the same dose restored autoregulation. The present findings suggest that the pituitary plays a role in hypothalamic blood flow autoregulation.

Animals↗

Effects of hypophysectomy, ovariectomy, and cycloheximide on specific binding sites for lactogenic hormones in rat liver.

We have previously shown that specific binding sites for lactogenic hormones are present at much greater levels in the liver membranes of female than of male rats. In the present studies [125I]iodo-hGH was used to study binding sites specific for lactogenic hormones in liver membranes. In male rats, a single injection of 2 mg estradiol valerate induced these binding sites. The induction was maximal by 9-12 days and was dose-dependent. Ovariectomy significantly reduced the specific binding of [125I]iodo-hGH from 9.7 +/- 0.7% in shamoperated to 6.9 +/- 0.3% in experimental rats (P less than 0.01) without a change in affinity. Fluctuations in specific binding of [125I]iodo-hGH were observed at different stages of the estrous cycle. Binding at estrus and diestrus I was significantly greater than at diestrus II and proestrus (P less than 0.05). The disappearance of binding sites following hypophysectomy was rapid, declining from 13.2 +/- 1.2% in intact rats to 6.0 +/- 0.8% and 2.2 +/- 0.4% 14 and 48 h, respectively, after surgery. In contrast, binding of insulin was slightly increased after hypophysectomy. Anti-estrogens (clomiphene, ICI 46,474, and nafoxidine) prevented the induction of binding sites in male rats given estradiol (E2). A single injection of 200 mug cycloheximide 11 days after an injection of 2 mg E2-valerate reduced binding by more than 90% in 3 h with a return to control levels by 48 h. The maximal decline in insulin binding was 54% during this entire period. These studies suggest that endogenous estrogen plays a role in regulating hepatic binding sites for lactogenic hormones. The level of these binding sites is critically dependent on the presence of an intact pituitary. The possible rapid turnover of these sites suggests that regulatory influences at the tissue level may have an important role in modulating hormone action.

Animals↗

Histological and histochemical study of the caudal neurosecretory system of the freshwater teleost Ompok bimaculatus (Bloch) with a note on its response to hypophysectomy and osmotic stress.

The caudal neurosecretory system in well developed in Ompok bimaculatus. It extends from 8th to the last caudal vertebra. In the last vertebra the spinal cord forms a distinct, lobate and highly vascular ventral urophysis where the neurosecretory fibers have perivascular endings forming a neurohaemal organ. In the anterior segment near the 8th preterminal vertebra the Dahlgren cells are large and sparsely distributed. In the posterior segment close to the urophysis they are small and densely arranged. The neurosecretory material (NSM) has affinity for acid stains but reacts negatively to Gomori's stain or to a reagent demonstrating SS/SH group. The Dahlgren cells have high RNA content in the cytoplasm indicating active protein synthesis. Histological evidence suggests that the caudal neurosecretory system of this species did not respond to hypertonic osmotic stress. However, immersion in deionized water is accompanied by hypertrophy of Dahlgren cells and depletion of NSM from the caudal neurosecretory system. Hypophysectomy results in initial hypertrophy of the Dahlgren cells followed by atrophic changes and depletion of NSM. Ninety days after hypophysectomy this system gradually reverts to normal.

Animals↗

Fatal pulmonary thromboembolism after successful transsphenoidal hypophysectomy for Cushing's disease.

We have reported the case of a 30-year-old woman with Cushing's disease who died of massive pulmonary thromboembolism 5 weeks after successful transsphenoidal hypophysectomy. Glucocorticoid excess appears to cause a hypercoagulable state, and consideration of this thromboembolic propensity and its potential duration after cure is indicated in all patients with Cushing's syndrome during the perioperative period. At the present time, we recommend the routine perioperative use of intermittent pneumatic compression in all patients with Cushing's disease or Cushing's syndrome.

17-Hydroxycorticosteroids↗

Abolishment of the positive feedback mechanism: a criterion for temporary medical hypophysectomy by LH-RH agonist.

The hypothalamic pituitary axis was studied in patients with an abnormal pattern of gonadotropin release during chronic treatment with LH-RH agonist. Two patients had PCOD and the third demonstrated the early luteinization phenomenon. Following a well-defined gonadotropin rise with initiation of LH-RH treatment, no further response was noted. Stabilization of the LH:FSH ratio in PCOD patients was noted after 4 weeks of treatment. Administration of both native LH-RH (100 micrograms) and intravenous pulsatile LH-RH did not evoke any rise in LH. In addition to the above LH-RH challenges, the positive feedback was examined by administration of estradiol benzoate (EB). The study demonstrated that, although the pituitary did not respond to any LH-RH challenge, it may still respond by a rise in LH following EB administration. Both functions of the hypothalamic pituitary axis should be examined in order to determine the state of medical hypophysectomy.

Administration, Intranasal↗

Palliation for advanced cancer of the breast, trans-septal-sphenoid subtotal hypophysectomy.

Subtotal hypophysectomy by the trans-septal-sphenoid approach was used for palliation in 23 cases of cancer of the breast. Of 18 patients in whom results could be evaluated, eight had palliation for various lengths of time. The other ten were not helped and four of them had complications from the operation. The average survival time for patients who were helped by the operation was longer than for those who were not.

Breast Neoplasms↗

Effects of ligation, orchidectomy, and hypophysectomy on expression of the Yf subunit of GST-P in principal and basal cells of the adult rat epididymis and on basal cell shape and overall arrangement.

BACKGROUND: Glutathione S-transferases (GSTs) are a family of isozymes that catalyze the conjugation of glutathione to various electrophilic compounds. Recently, the Yf subunit of GST-P, found in high concentrations in the epididymis, has been immunolocalized within epithelial principal and basal cells of this tissue. In order to determine which factor(s) were involved in the regulation of expression of this protein, adult rats were orchidectomized and treated with or without testosterone implants, ligated or hypophysectomized. METHODS: The epididymides were fixed by perfusion with Bouin's fixative and examined with an anti-Yf antibody using light microscope immunocytochemistry. RESULTS: In normal untreated animals, principal cells were reactive in the distal initial segment, intermediate zone and caput epididymidis, but unreactive in all other epididymal regions. Ligation of the efferent ducts up to day 14 had no effect on expression of the Yf protein in principal cells of any region. The staining pattern was comparable to that observed in normal untreated animals suggesting that luminally derived testicular factors were not involved in regulation of Yf expression. Following orchidectomy, principal cells became unreactive by day 14 in all epididymal regions. However, administration of testosterone to orchidectomized animals prevented the loss of reactivity seen in principal cells of the distal initial segment, intermediate zone, and caput epididymidis, suggesting that expression of the Yf protein in principal cells of these regions is regulated by circulating testosterone. In contrast, basal cells after each experimental treatment including hypophysectomy maintained the exact staining pattern observed in normal untreated animals, i.e., they were intensely reactive in the proximal initial segment, distal caput, corpus, and proximal cauda regions, suggesting that expression of the Yf protein in these cells does not require factors derived from the testis or pituitary gland. However, a change in the shape and arrangement of basal cells was noted following each treatment. These cells transformed from flattened hemispherical cells showing thin elongated lateral processes to large bulbous, dome-shape cells closely packed together and showing only a few short lateral processes. CONCLUSIONS: In basal cells, expression of the Yf protein is not regulated by testicular or pituitary factors, whereas expression in principal cells is regulated by circulating testosterone. Due to the decrease in size of the epididymal tubules after each treatment, it is postulated that the shape and arrangement of basal cells in normal untreated animals are governed in part by the volume and pressure exerted upon the tubules by luminal fluids and spermatozoa derived from the testis.

Animals↗

Hypophysectomy in the treatment of disseminated prostate carcinoma.

Seventeen patients suffering severe pain secondary to disseminated prostate cancer were subjected to hypophysectomy. Prolonged remission of pain and increased survival duration appeared to be consequent to obtaining objective signs of tumor regression. Patients who had only subjective improvement had significantly shorter periods of remission and survival. Patients with hematocrits less than 30% and patients demonstrating evidence of liver involvement did not obtain objective remissions.

Aged↗

Evaluation of transsphenoidal hypophysectomy in the management of patients with advanced malignant melanoma.

Transsphenoidal hypophysectomy was performed in 13 patients with advanced malignant melanoma. Although three minor responses were observed, there were no complete or partial responses. All three patients with bone pain had a decrease in discomfort lasting 1-2 months. All five patients with minor responses or stable disease had postoperative decreases in the excretion of the dihydroxyphenylalanine (DOPA) metabolite 3-O-methyldopamine; all but one patient with clinical progression had postoperative increases in excretion. Average survival of those whose postoperative excretion fell (143 +/- days; range, 60-217+) was significantly longer (P less than 0.004) than that of those whose postsurgical values rose (30 days; range, 15-58).

Adult↗

Hydromineral balance in the chick embryo: effects of hypophysectomy.

The developing chick embryo exhibits a regular pattern of accumulation and reabsorption of fluid in its extraembryonic compartments. Fluid volume (measured by dye dilution) peaks at Day 14 in both the allantois (12.4 ml) and the amnion (5.1 ml). The standard experimental procedure of removing 2 ml of albumen at 33-36 hr of incubation does not alter this pattern, but leads to a maximum decrease in fluid volume of ca. 1 ml in both amniotic and allantoic compartments. Although [Na] and [Cl] remain essentially constant in the serum, they steadily decrease in the allantois (remaining substantially below serum levels). In the amnion, [Cl] is maintained above that of serum, whereas [Na] falls below serum [Na] by Day 14. In the Day 12 (stage 38) embryo, hypophysectomy (HX) causes a substantial increase in the allantoic fluid volume and [Na] and [Cl], thus resulting in a 166% increase in total Na and Cl over that of sham-operated embryos. By contrast, HX did not alter amniotic fluid volume, although it did decrease [Na] and to a lesser degree, [Cl]. Serum [Na], but no [Cl], was reduced by HX. HX abolished the normally steep ionic gradients maintained between the allantois and both serum and amnion. Thus, the most dramatic effects of HX at Day 12 are on the allantois, which accumulates both Na and Cl at the expense of the amnion and serum. This suggests that pituitary hormones may normally act by Day 12 to reduce urinary volume and electrolyte excretion and/or to increase fluid and electrolyte reabsorption from the allantois.

Allantoin↗

Growth, differentiation, and function of the testes in the toad Bufo bufo bufo (L.), with special reference to regulatory capacities: effects of unilateral castration, hypophysectomy, and excision of Bidder's organs.

Function and compensatory growth of the testis have been studied in male toads of varying ages, ranging from postmetamorphosis to adults. All experiments lasted 2 months, starting about September 1. Spermatogenesis was normal in sexually immature, 1-year-old toads. The fastest growing young toads developed secondary sex characteristics, the thumbpads, during the experiment. The data suggest that size is more influential than age in determining the onset of sexual maturation. But body size is not the only factor which influences sexual maturation. The growth response of the remaining testis to unilateral castration decreased with increasing age and size of the toads. Two months after operation the remaining testis had reached the size of two testes in the young toads, whereas the testis showed no significant compensatory growth in the adult-sized toads, whether sexually immature or mature. Hypophysectomy reduced body growth in young toads and prevented a testicular growth response to unilateral castration. Young toads, but no adults, with excised Bidder's organs had larger testes than the control toads. In hypophysectomized, young toads spermatogenesis was still active 2 months after the operation.

Animals↗