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PubMed1984

Suppression of residual oestrogen production with aminoglutethimide in women following surgical hypophysectomy or adrenalectomy.

In postmenopausal women with breast carcinoma, plasma and urinary oestrogens remain detectable following surgical adrenalectomy or hypophysectomy. These residual oestrogens could result from absorption of exogenous steroids, from endogenous production, or from a combination of these two sources. To determine whether endogenous production contributes to this oestrogen pool, we administered a potent steroidogenesis inhibitor, aminoglutethimide (AG), to women with breast carcinoma following hypophysectomy or adrenalectomy. Plasma and urinary oestrogens were measured with radioimmunoassays developed to provide appropriate sensitivity. In five women treated after initial hypophysectomy (hypox), plasma oestrone fell from 66 + 28 pg/ml (hypox) to 9.1 +/- 2.4 pg/ml (hypox and AG) and oestradiol decreased from 8.3 +/- 1.8 pg/ml to 2.5 +/- 0.69 pg/ml. Similar decrements in urine oestrone (U-E1) and ostradiol (U-E2) were observed (U-E1 hypox: 2.25 +/- 0.71 microgram/24 h 0.071 +/- 0.015 microgram/24 h hypox and AG; U-E2 0.47 +/- 0.12 micrograms/24 h hypox to 0.124 +/- 0.015 hypox and AG, P less than 0.05 for all). Similar significant reductions in plasma oestrone and oestradiol were observed in four women treated with aminoglutethimide following surgical adrenalectomy. While the levels of urinary oestrogens also fell in these patients, the differences were not statistically significant. In response to the decrements in oestrogen levels induced by AG, 2/5 women in the post-hypophysectomy group and 2/4 in the post-adrenalectomy group experienced partial objective tumour regression. These observations indicated that the residual oestrogens produced after surgical adrenalectomy or hypophysectomy, even though made in small quantities, were nonetheless biologically active. We conclude that endogenous production of oestrogens in extragonadal and extra-adrenal sites occurs after major surgical endocrine ablation in women with breast carcinoma. Additional exogenous oestrogen sources can not be excluded.

Adrenalectomy↗
PubMedDate not supplied

Transsphenoidal hypophysectomy in beagle dogs: evaluation of a microsurgical technique.

OBJECTIVE: Assessment of a microsurgical technique for transsphenoidal hypophysectomy in dogs. STUDY DESIGN: Prospective study using physical examination, pituitary function testing, computed tomography (CT), and histological examination at autopsy. ANIMALS OR SAMPLE POPULATION: Eight laboratory beagle dogs. METHODS: Pituitary function was assessed before and at 10 weeks after hypophysectomy by combined administration of four releasing hormones (anterior pituitary), administration of haloperidol (pars intermedia), and infusion of hypertonic saline (posterior pituitary). RESULTS: CT imaging enabled accurate preoperative localization of the pituitary. Appropriate positioning and surgical technique facilitated exposure of the pituitary and its extraction without hemorrhage. Postoperative recovery was generally uncomplicated. None of the eight dogs had somatotropic, gonadotropic, lactotropic, melanotropic, or posterior pituitary responses to stimulation at 10 weeks after hypophysectomy. Four dogs (ACTH nonresponders) also had no corticotropic response and four (ACTH responders) had small but significant responses in the combined anterior pituitary function test. Adrenocortical atrophy was more pronounced in the ACTH nonresponders than in the responders. No residual pituitary tissue was found along the ventral hypothalamic diencephalon but nests of pituitary cells were found embedded in fibrous tissue in the sella turcica. CONCLUSIONS: The surgical technique proved to be safe and effective. Microscopic nests of pituitary cells in the sella turcica may be responsible for residual corticotropic response to hypophysiotropic stimulation after hypophysectomy. CLINICAL RELEVANCE: The surgical technique may be used in the treatment of dogs with pituitary-dependent hyperadrenocorticism. The corticotropic response is the most sensitive criterion in assessing completeness of hypophysectomy in dogs.

Adrenocortical Hyperfunction↗
PubMedDate not supplied

Canine hypophysectomy using a ventral paramedian approach.

OBJECTIVE: To evaluate the degree of pituitary exposure, completeness of hypophysectomy, and perioperative morbidity associated with an alternative paramedian surgical approach and excisional technique for the canine pituitary gland. STUDY DESIGN: Experimental imaging, surgical, and endocrinologic study. ANIMAL POPULATION: Nine healthy, purpose-bred Beagle dogs. METHODS: Surgical landmarks for the pituitary were determined by computed tomography (CT), and then using a ventral paramedian approach medial to the rami of the mandible, the pituitary was exposed and removed en bloc by manipulation and ultrasonic aspiration. Efficacy of the procedure was evaluated using endocrinologic and pathologic observation. RESULTS: CT images allowed the precise location of surgical landmarks for hypophysectomy. Statistically significant decreases in secretion of all measured pituitary hormones except adrenocorticotropic hormone (ACTH) occurred after hypophysectomy. Despite the absence of gross evidence of residual pituitary tissue, immunohistochemical staining revealed residual pituitary cells in the sella turcica of most dogs. CONCLUSION: CT imaging and a paramedian approach facilitated surgical access to the pituitary gland by a transoral technique; however, use of an ultrasonic aspirator removed all visible pituitary glands but left cellular remnants capable of ACTH secretion in the sella turcica. CLINICAL RELEVANCE: Although this technique did not result in complete hypophysectomy, clinical use in dogs with pituitary-dependent hyperadrenocorticism is warranted because the goal is not complete hypophysectomy but removal of a pituitary tumor.

Adrenocortical Hyperfunction↗
PubMed1979

In vitro effects of growth hormone on protein synthesis and amino acid transport in the rat diaphragm after acute hypophysectomy.

The effects of growth hormone (GH) in vitro on phenylalanine-14C incorporation to assess protein synthesis and on alpha-aminoisobutyric-1-3H accumulation to measure amino acid transport in the diaphragm muscle of the rat were investigated 2, 6 and 24 h after hypophysectomy or sham-operation. In hypophysectomized animals protein synthesis was depressed. GH in vitro was without effect 2 h after hypophysectomy but stimulated protein synthesis 6 and 24 h after the operation. Six hours after hypophysectomy amino acid transport was enhanced and further stimulated by GH. After 24 h amino acid transport was depressed but was stimulated to normal levels by GH. Six hours after sham-operation protein synthesis was depressed, but was stimulated by GH. After 24 h protein synthesis was normalized and GH was without effect. GH did not influence amino acid transport after sham-operation. Plasma levels of GH were undetectable after hypophysectomy, markedly depressed 2 and 6 h after sham-operation, but normal after 24 h. It is concluded that tissue responsiveness to GH develops a few hours after hypophysectomy.

Amino Acids↗
PubMed1985

Changes in growth hormone binding and metabolic effects of growth hormone in rat adipocytes following hypophysectomy.

Growth hormone (GH) binding and the effect of GH and insulin on glucose metabolism in rat adipocytes were studied at various time periods following hypophysectomy. Male rats were hypophysectomized at 33-34 days of age. After 6 h, 20 h or 3, 7 and 14 days adipocytes were prepared from epididymal fat pads by mild collagenase digestion (0.5 mg X ml-1, 60 min, 37 degrees C). Glucose metabolism was studied by determining the production of CO2 from [14C]glucose and the incorporation of [14C]glucose into lipids. GH binding was measured in cell aliquots using [125I]hGH. No difference in GH binding to adipocytes was observed between control rats and rats hypophysectomized or sham-operated 6 h earlier. GH binding was significantly decreased 20 h after hypophysectomy and declined further with time after hypophysectomy. Adipose tissue from normal rats is usually refractory to the insulin-like effect of GH. Adipocytes isolated from normal rats were, however, usually responsive to GH immediately after cell isolation, suggesting that refractoriness to the insulin-like effect of GH was lost during the time required for the preparation of adipocytes. The magnitude of the response to GH in adipocytes progressively declined with time after hypophysectomy. The decreased responsiveness to GH with time after hypophysectomy parallelled the decrease in GH binding. The results suggest that the pituitary, directly or indirectly, is necessary for the maintenance of GH binding sites in adipose tissue and that these binding sites are related to the insulin-like effect of GH.

Adipose Tissue↗
PubMed1977

The effects of bilateral adrenalectomy or hypophysectomy of the foetal lamb in utero.

1. Foetal hypophysectomy or bilateral adrenalectomy, carried out in utero at about 100 or 125 days gestation respectively, increased the length of gestation in sheep. It was confirmed that pregnancy was not prolonged significantly if hypophysectomy or adrenalectomy was carried out on one of a pair of twins. The hypophysectomized foetus was, however, smaller and the adrenalectomized foetus larger, than the unoperated twin. 2. In about half of the previously operated foetuses intravascular catheters were inserted into both mother and foetus, either at about 125 days, for a comparison with normal catheterized foetuses, or during the post-mature period. Both adrenalectomized and hypophysectomized foetuses appeared to have little resistance to stress or infection and the majority survived only 1-2 weeks after the insertion of catheters. 3. Maternal peripheral plasma oestrogen, progesterone and corticosteroid concentrations did not appear to be altered by either foetal hypophysectomy or adrenalectomy and were maintained in the normal range during prolonged gestation. 4. Foetal plasma oestrogen concentrations were significantly lower after hypophysectomy or adrenalectomy than values found in control lambs. Plasma progesterone values were low in all three groups of foetuses. 5. Plasma corticosteroid concentrations after foetal hypophysectomy (12-6 ng/ml.) or adrenalectomy (14-7 ng/ml.) were in the same range as the values for control lambs before the pre-partum rise (14-6 ng/ml.). However, there was a small but significant maternal-to-foetal plasma corticosteroid gradient in the two operated groups whereas this difference was not found in the control animals. 6. Tissue glycogen concentrations were measured in non-catheterized adrenalectomized and hypophysectomized foetuses. In these two groups, whether examined before 149 days or after prolonged gestation, liver glycogen concentrations were 30-40% of those in non-catheterized control foetuses at term. In other respects there was little apparent difference between adrenalectomized and control foetuses. 7. Hypophysectomized foetuses had significantly higher glycogen concentrations in heart, skeletal muscle and lung compared with control or adrenalectomized lambs. Plasma glucose and fructose values were also low in this group compared with control foetuses.

Adrenal Cortex Hormones↗
PubMed1971

Further observations concerning the effects of hypophysectomy on the gastric mucosa of the rat.

Hypophysectomy in rats markedly reduced the weight and surface area of the stomach as well as the volume (mass) of the gastric mucosa and the total parietal and total peptic cell populations. The parietal cell population was reduced by about 50%, and this effect was due entirely to the reduction that occurred in the total surface area of the stomach (50%); the average number of parietal cells per unit area, which reflects the number of parietal cells in the gastric glands, was not affected. The peptic cell population was reduced by about 90%, the factors responsible being a reduction in the average number of peptic cells per unit area (70%) as well as the reduction that occurred in the surface area of the stomach. The disproportionate effect of hypophysectomy on the cell populations was thus due to the reduction in the number of peptic cells per unit area; this effect implies that hypophysectomy had caused a reduction in the number of the peptic cells in the gastric glands.Whatever the mechanisms involved these results were due to a direct effect of pituitary deprivation on the stomach, since they could not be accounted for simply by the inhibition of somatic growth that follows hypophysectomy in rats. Thus the experiment included a group of sham hypophysectomized rats whose somatic growth was inhibited to the same extent as that of the hypophysectomized animals by deliberate underfeeding. While underfeeding reduced the surface area of the stomach (20%) and the total peptic cell population (25%), as well as exerting a marginal effect on the parietal cell population, these effects were much smaller in magnitude than those of hypophysectomy; moreover underfeeding did not affect the number of peptic cells in the gastric glands. The results confirm that the pituitary gland exerts a strong influence on the growth of the gastricmucosa.

Adrenal Glands↗
PubMed1977

Development in calves and heifers after hypophysial stalk transection or hypophysectomy.

Growth was inhibited markedly in prepuberal bull and heifer calves after either hypophysial stalk transection or hypophysectomy as compared with that found in sham-operated calves or in unoperated calves. Male mounting behavior and evidence of puberal estrous behavior were lost or undetected after hypophysial stalk transection or hypophysectomy. Testes regressed, contained few spermatogonia and interstitial cells, and lacked spermatogenesis. Epithelial cells of seminal vesicles, bulbourethral glands, and prostate were cuboidal, indicating inadequate testicular androgen. Atresia of numerous ovarian follicles and reduced ovarian weight occurred in hypophysectomized heifer calves. Graafian follicles regressed after hypophysial stalk transection of sexually mature heifers, but ovaries responded to pregnant mare serum and human chorionic gonadotropin by follicular development, ovulation, and formation of multiple corpora lutea. Thyroid and adrenal gland weights decreased and adrenal cortices atrophied after hypophysectomy, but not after stalk transection. Thyroid glands contained colloid-filled follicles with flattened epithelial cells; atrophy was more extensive after hypophysectomy. Hypophysial stalk transection or hypophysectomy severely depresses growth and arrests sexual development in young calves, but in mature animals exongenous gonadotropins can sustain gonadal function.

Adrenal Glands↗
PubMed1979

Hypophysectomy and saralasin on mesenteric vasoconstrictor response to vasopressin.

The dose-response relationship of the mesenteric resistance vessels to vasopressin was studied in anesthetized laparotomized cats before and after hypophysectomy and again during the plateau phase of the response to a prolonged infusion of [Sar1-Ala8] angiotensin II (saralasin), a competitive antagonist of angiotensin II. Hypophysectomy and saralasin each caused an increase in superior mesenteric arterial conductance. Before hypophysectomy infusion of 0.5 mU/(min.kg) of vasopressin caused mesenteric conductance to decrease from 0.168 to 0.156 ml/(min.kg.mmHg), a change of only 0.012 units. After hypophysectomy, the same dose reduced conductance from 0.227 to 0.179 mU/(min.kg.mmHg), a change of 0.048 units. During the plateau phase of the response to saralasin, 0.5 mU/(min.kg) of vasopressin reduced conductance from 0.281 to 0.201 ml/(min.kg.mmHg), a change of 0.079 units. Hypophysectomy and saralasin had little effect on the mesenteric vasoconstrictor response to high doses of vasopressin (2.0-10 mU/(min.kg). The ineffectiveness of low doses of vasopressin on the mesenteric resistance vessels of the intact anesthetized, surgically stressed animal may be due in part to the already constricted state of the bed caused by endogenous vasopressin and angiotensin and in part due to an opposing vasodilator influence, the reflex withdrawal of the vasoconstrictor effect of endogenous vasopressin.

Angiotensin II↗
PubMed1984

Effects of hypophysectomy on tissue alkaline phosphatase in the rat.

To examine the effect of hypophysectomy on tissue alkaline phosphatase (EC 3.1.3.1) activity, studies were performed on mature rats. Hypophysectomy reduced the alkaline phosphatase activity in duodenum, kidney, and femoral bone. The decrease of alkaline phosphatase was greater in the intestine than in other organs studied. Intestinal alkaline phosphatase fell rapidly within 4 days post-hypophysectomy. In contrast, bone and kidney alkaline phosphatase activity had an initial lag period for 4 days after the hypophysectomy. Serum alkaline phosphatase also declined after hypophysectomy. The bone isoenzyme of serum alkaline phosphatase was reduced to a greater extent than the intestinal isoenzyme.

Alkaline Phosphatase↗
PubMed1978

Effect of hypophysectomy of cholesteryl ester synthesis and hydrolysis in testes and on serum lecithin-cholesterol acyltransferase activity in rats.

Studies are reported of the effect of hypophysectomy on cholesterol esterase activity of testicular tissue and serum lecithin-cholesterol acyltransferase (LCAT) activity in rats. The testes of male Sprague-Dawley rats of 200-255 g were excised from animals sacrificed at 3, 7, and 15 days after hypophysectomy. Assays for cholesterol-esterifying and hydrolytic activities of the testicular tissues of these animals, compared to control animals, showed that hypophysectomy decreased both cholesteryl ester synthesis and hydrolysis. Hydrolytic activity was affected to a greater extent than esterifying activity. LCAT activity was significantly decreased by hypophysectomy compared to that of control animals. Although serum LCAT and testicular cholesterol esterase activities were decreased, the overall effect of hypophysectomy produced an increase in the level of serum cholesterol and cholesteryl esters. It is suggested that the role of essential fatty acids (EFA) in testicular function is related to the utilization of cholesteryl esters in androgen synthesis.

Animals↗
PubMed1985

The effects of hypophysectomy and administration of pituitary hormones on luteal function and uptake of high density lipoproteins by luteinized ovaries and adrenals of the rat.

The role of plasma lipoproteins and hypophyseal hormones in the maintenance of progesterone secretion by the rat corpus luteum was investigated. In the first experiment, rats were treated daily from days 1-6 of pregnancy with 5 mg/kg 4-aminopyrozolopyramidine (4APP), a blocker of hepatic lipoprotein secretion, or with 5 mg/kg 4APP and 1 or 2 mg ovine PRL or 0.1 ml 0.5% phosphoric acid (4APP vehicle). The administration of 4APP reduced serum cholesterol and progesterone levels on days 2-6 of pregnancy and ovarian progesterone on day 6. The reduced progesterone secretion had no effect on embryo implantation. PRL, in the doses used, was incapable of abrogating the effects of 4APP on circulating or ovarian progesterone levels. Ovaries and adrenals, but not kidneys, of pseudopregnant rats exhibited specific and saturable uptake of porcine high density lipoprotein (HDL). Time-course studies indicated that the uptake of HDL was rapid in ovaries compared to that in adrenals. Ovaries from rats not only exhibited uptake of porcine HDL, but also were capable of using it for progesterone synthesis. Immature rats were assigned to 7 groups of 16 rats each; 8 rats from each group received 4 mg/kg 4APP, and 8 received 4APP vehicle from day 1 of pseudopregnancy. Four groups underwent hypophysectomy on day 1 and received one of the following: 0.1 mg (30 IU/mg) ovine PRL, 0.1 mg ovine LH or 0.1 mg synthetic ACTH daily, or no replacement therapy. Three sham-hypophysectomized groups received 0.1 mg PRL or LH twice daily or no hormone treatment. On day 5 of pseudopregnancy, rats received intravascular HDL, as described above, and were killed 1 h later. Treatment with 4APP increased the adrenal uptake of HDL, but ovarian uptake was not different from that in the control group. Hypophysectomy reduced both adrenal and ovarian uptake of HDL. In adrenals only ACTH at the dose employed ameliorated reduction of HDL uptake induced by hypophysectomy, while in the ovaries, both PRL and LH reversed the effect of hypophysectomy. The effect of PRL on uptake was specific to [125I]HDL and did not alter [125I]albumin uptake. It is concluded that: 1) hypophysectomy reduces HDL uptake in the luteinized rat ovary; and 2) PRL and LH replacement therapy maintain ovarian uptake of HDL, suggesting a direct effect of these luteotropins on lipoprotein uptake.

Adrenal Glands↗
PubMed1975

Hypophysectomy of the tammar wallaby, Macropus eugenii: surgical approach and general effects.

A technique of hypophysectomy and regimes of pre- and post-operative care were developed for the tammar wallaby, Macropus eugenii, to a stage when animals can survive the operation with little apparent stress. Thyroid and adrenal gland weights declined after hypophysectomy, especially within the first 20-30 days. Changes in the adrenal cortex after hypophysectomy suggested that this region may have a zonal organization different from that in eutherian mammals. The reproductive tracts of males and females lost weight rapidly after hypophysectomy. Eleven plasma parameters were studied for the effects of hypophysectomy. There was a reduction in sodium and chloride and a tendency to higher potassium levels, reflecting inadequate adrenal cortical function. Calcium and total protein values remained unaffected, but inorganic phosphate, glucose and cholesterol were depleted, and a less significant depletion in blood urea, nitrogen and uric acid was evident.

Adrenal Glands↗
PubMed1975

Effects of hypophysectomy and short-term growth hormone replacement on insulin release from and glucose metabolism in isolated rat islets of Langerhans.

The effects of hypophysectomy and short-term GH replacement on insulin release and on some aspects of glucose metabolism in isolated rat islets of Langerhans were investigated. The effects on body, pancreas and adrenal gland weights, and on the levels of blood plasma constituents were also measured. Three to four weeks after hypophysectomy the early and late phases of insulin release from islets incubated with high concentrations of glucose, but not with low concentrations of glucose or with xylitol, leucine, arginine, tolbutamide, citrate or butyrate, were significantly lowered. Short-term GH replacement partially reversed the depression in glucose-stimulated insulin release. This reversal effect was not dependent on the increase in body weight of rats after GH replacement when the fall in adrenal gland but not in pancreas weight was also reversed. Nine out of the 12 plasma constituents measured, including glucose, were maintained in the control range of levels, but albumin, inorganic phosphate and urea nitrogen levels were altered after hypophysectomy or GH replacement. Three to four weeks after hypophysectomy, total glucose oxidation and glucose utilization by the islets were slightly depressed. Hypophysectomy appeared to slow down glucose 6-phosphate utilization in the islets. However, the functional capacity of the glucose phosphorylating, glucose-6-phosphate and 6-phosphogluconate dehydrogenase activities were not changed. Short-term GH replacement caused improvements in these islet functions.

Adrenal Glands↗
PubMedDate not supplied

Hypophysectomy and injections of high doses of estrogens inhibit the growth of ovary-independent rat mammary carcinomas.

Estrogen receptor-negative, 7, 12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary carcinoma (TF1357) grew equally well in ovariectomized females, ovariectomized females with thyroidectomy and ovariectomized females given injections of Tamoxifen (0.1 mg/day), Medroxyprogesterone acetate (8 mg/day) or CB-154 (1 mg/day). However, the growth of TF1357 was inhibited markedly by injections of a very large amount of 17 beta-estradiol (1 mg/2 days) and also by hypophysectomy. The growth of estrogen receptor-positive, DMBA-induced rat mammary carcinoma (8K2401) was also almost completely inhibited by hypophysectomy and injections of high doses of 17 beta-estradiol, while 8K2401 grew well in castrated males. Secretory changes characterized by vacuolation in cytoplasm were observed in 8K2401 cells in castrated males with injections of high doses of estrogen but these changes were not found in 8K2401 cells in castrated males with hypophysectomy or in TF1357 cells in ovariectomized females which had had hypophysectomy or injections of high doses of estrogen. These observations suggest that hypophysectomy and/or injections of high doses of estrogen may be effective treatment for breast cancer unresponsive to ovariectomy or injections of antiestrogen drugs.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

The effect of hypophysectomy on thymic aging in mice.

Surgical removal of the pituitary (hypophysectomy) followed by endocrine supplementation in middle-aged rats has been reported to reverse immunologic decline with age. We attempted to confirm and extend these reports by using a well-defined and readily available mouse model system. Hypophysectomy and endocrine supplementation in 8- to 9-mo-old C57BL/6J (B6) male retired breeder mice improved some, but not all, T dependent immune functions tested at 15 mo of age. In hypoxed mice, spleen cell proliferation in response to phytohemagglutinin (PHA) in vitro, and delayed type hypersensitivity (DTH) responses to sheep red blood cells (SRBC) measured by footpad swelling improved to levels shown by young controls. Direct anti-SRBC plaque-forming cell (PFC) responses by spleen cells, and serum agglutination responses against SRBC were not improved. Hypoxed mice had larger thymuses and much higher ratios of cortex-medulla areas than did age-matched controls. Hair regrowth after shaving was much faster in hypoxed mice. Nevertheless, hypophysectomy reduced mean and maximum longevities. These results conflict in several ways with the previously reported studies in rats, in which direct PFC responses and maximum longevities were improved by this treatment. There have been no previous studies of the effect of hypophysectomy and endocrine supplementation on thymic aging in mice, nor has it previously been reported that this treatment causes improvements in PHA and DTH responses and in thymic morphology. These effects show that at least some aging processes are reversible in aging individuals. They also suggest that hypophysectomy of middle-aged mice will be useful for studying neuroendocrine and thymic interactions that occur during the aging process.

Aging↗
PubMed1994

Reorganization of neural peptidergic systems in the median eminence after hypophysectomy.

Earlier studies have shown the formation of a novel neural lobe after hypophysectomy, an experimental manipulation that causes transection of neurohypophyseal nerve fibers and removal of pituitary hormones. The mechanisms that underly this regenerative process are poorly understood. The localization and number of peptide-immunoreactive (-IR) fibers in the median eminence were studied in normal rats and in rats at different times of survival after hypophysectomy using indirect immunofluorescence histochemistry. The number of vasopressin (VP)-IR fibers increased in the external layer of the median eminence in 5 d hypophysectomized rats. Oxytocin (OXY)-IR fibers decreased in the internal layer and progressively extended into the external layer. At long survival times (9 and 16 months) both VP- and OXY-IR fibers had a bilayered distribution occupying both the external and internal layers. Double-labeling experiments combining VP and tyrosine hydroxylase antisera as well as OXY and growth hormone-releasing factor antisera showed that injured neurosecretory fibers growing into the external layer displaced fibers from parvocellular cells originally located there. As a result, there was essentially an inversion in the distribution of these fibers within the median eminence. Galanin (GAL)- and cholecystokinin (CCK)-IR fibers exhibited a similar pattern of distribution after the lesion. Thus, after 5 d there was an increase in GAL- and CCK-IR fibers in the internal layer. At 14 and 30 d, the number of GAL- and CCK-IR fibers progressively decreased, but after longer survivals (9 and 16 months) there was a dramatic reappearance. Dynorphin (DYN)-LI showed a dramatic increase at all levels of the median eminence at short survival times after hypophysectomy, followed by a subsequent decrease to a final stage of a few, strongly immunoreactive fibers in the external layer at longer survival times. Vasoactive intestinal polypeptide (VIP)- and peptide histidine-isoleucine (PHI)-IR fibers in hypophysectomized animals had already contacted portal vessels 5 d after hypophysectomy, and from then on progressively increased in numbers. Finally, most of the peptide fibers described above formed dense innervation patterns around the large blood vessels along the lateral borders of the median eminence. The present results show that hypophysectomy induces a wide variety of changes in hypothalamic neurosecretory fibers. Not only is the expression of several peptides in these fibers modified following different survival times, but a reorganization of the distribution of immunoreactive fibers within the median eminence is demonstrated. The hypothesis is raised that regeneration of injured neurosecretory fibers may be dependent on changes in the expression of peptides possessing trophic actions.

Animals↗
PubMed1994

Effects of hypophysectomy on TRH and its related peptides concentrations in various rat organs.

The effects of hypophysectomy on thyrotropin releasing hormone (TRH), TRH-glycine (TRH-Gly) and pre-pro-TRH (178-199) concentrations in the rat hypothalamus, cerebrum, cerebellum, brain stem, stomach and retina were studied 7 days after the operation. The hypophysectomized rats were administered a single i.p. injection of T4 (500 micrograms/kg), T3 (100 micrograms/kg) or bovine TSH (1.25 IU/kg), and 5 rats of each subgroup were decapitated at 4 hours later. After hypophysectomy, TRH-Gly and pre-pro-TRH (178-199) concentrations in the hypothalamus increased significantly and TRH concentrations decreased after hypophysectomy. After the injection of T4, T3, TRH or TSH TRH-Gly and pre-pro-TRH (178-199) concentration in the hypothalamus of hypophysectomized rats decreased significantly, while that of TRH significantly increased. No changes in TRH, TRH-Gly and pre-pro-TRH (178-199) concentration in other tissues were observed after hypophysectomy or hormone treatment. The findings suggest that hypophysectomy stimulated TRH synthesis and release in the hypothalamus, that TRH, TSH, T3 and T4 regulate hypothalamic TRH levels, and that pro-TRH synthesis in the tissues except the hypothalamus may not be regulated by thyroid hormone.

Animals↗