Effects of hypophysectomy and hypophysectomy plus growth hormone on secretin release and on concentrations of secretin in the duodenal mucosa.
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Structural response of the hamster Sertoli cell to hypophysectomy: a correlative morphometric and endocrine study.
Reproductively active hamsters were hypophysectomized and examined 6 or 20 days later in a combined morphometric and endocrine study of the Sertoli cell to determine 1) the morphological and endocrine effects of hypophysectomy of both short- and long-term duration, 2) if regression of Sertoli cells after hypophysectomy in a seasonal breeder resembles regression due to seasonal changes, and 3) if effects of hypophysectomy in a seasonal breeder are equivalent to the effects of hypophysectomy in a nonseasonal breeder. Six days after hypophysectomy, at a period when germ cell degeneration is first noted, there was a significant decrease in testis weight, interstitial space, tubule diameter and length, volume of seminiferous tubule, and tubular lumen. There were no significant changes in Sertoli cell nuclear and cytoplasmic volume although cell surface area was decreased significantly. Most organelles exhibited no significant change in volume or surface area except for secondary lysosomes which expectedly increased in volume as the result of phagocytosis of germinal cells. Thus at an early time period when functional changes in germ cells and Leydig cells are clearly evident (Russell et al. [1992] Endocrinology), the Sertoli cell shows minimal changes. Twenty days after hypophysectomy, the cell, nuclear and cytoplasmic volumes and surface area of the Sertoli cells, and volumes and surface areas of nearly all organelles were significantly decreased from values measured in normal and in short-term hypophysectomized hamsters. The exceptions were the total volumes of lipid which increased significantly and lysosomes which were similar to normal but significantly lower than short-term hypophysectomized animals. The long-term hypophysectomized hamster Sertoli cell, like that of the short-day hamster (Sinha Hikim et al. [1989b] Endocrinology, 125:1829-1843) is structurally regressed as a whole rather than exhibiting selective decreases in cellular and subcellular components. The size of the Sertoli cell in pituitary-intact, long- and short-term hypophysectomized animals showed positive and significant correlations with the volumes and surface areas of all its cytoplasmic organelles except the volume of lipid which showed a negative, significant correlation. Comparisons of long-term hypophysectomized hamsters (in long-day light exposure) and short-day exposed animals (Sinha Hikim et al. [1989b] (Endocrinology, 125:1829-1843) suggested that hypophysectomy, in general, resulted in similar, but slightly more severe regressive changes in the testis and germ cell population than those seen during seasonal regression.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Hypophysectomy for stage IV breast cancer.
Transnasal, transsphenoidal microsurgical hypophysectomy is a useful therapeutic procedure for patients with Stage IV breast cancer which can be peformed in selected patients with minimal morbidity and mortality. Functionally complete hypophysectomy can be accomplished with regularity, and anything less than this is considered to be a technical failure despite the fact that remissions may occur after incomplete hypophysectomy. In view of the recent outstanding results with antiestrogen therapy in patients with breast cancer, we recommend this as the initial treatment in those patients who are good candidates for endocrine therapy. Hypophysectomy has been shown to induce improvement after antiestrogen treatment, particularly in those patients who have had an initial response to antiestrogens as well as in a few patients who failed to benefit. Estrogen receptor measurements in the tumor tissue have been shown to be useful in selecting patients for hypophysectomy as well as for antiestrogen therapy. Prolactin receptors have been found in about 50 per cent of human breast cancers, and their potential usefulness in selecting patients for hypophysectomy is being explored. Hypophysectomy is a definitive therapeutic procedure that should not be used as a last resort in the terminally ill patient.
Adrenalectomy↗
Prolactin dynamics following transphenoidal hypophysectomy for metastatic carcinoma of the breast.
In nine patients who had undergone trans-sphenoidal hypophysectomy, prolactin dynamics were studied with intravenous thyrotropin releasing hormone (TRH). Residual prolactin secretory reserve was demonstrated in seven. Five patients were TRH tested both before and after trans-sphenoidal hypophysectomy. Hypophysectomy did not alter base line prolactin concentration but did decrease prolactin response to TRH from 55 ng/ml to 21 ng/ml (p less than 0.001). Post-hypophysectomy L-Dopa suppressed baseline prolactin concentrations to undetectable levels. There was no correlation between alterations in prolactin dynamics and tumor response to hypophysectomy. Trans-sphenoidal hypophysectomy is not effective in ablating prolactin secretion and serious doubts are raised about the role of altered prolactin dynamics in inducing breast cancer remission.
Breast Neoplasms↗
Effect of hypophysectomy on rat preadipocyte replication and differentiation.
The effects of hypophysectomy, which results in decreased fat pad weight, fat cell number, and new fat cell formation, on preadipocyte replication were examined. Perirenal and epididymal preadipocytes were cultured from hypophysectomized, sham-operated and unoperated 3-month-old rats. In cloned preadipocytes, hypophysectomy resulted in a 19% decrease in cloning efficiency and a 60% reduction in cell number after 3 weeks in culture. Perirenal cells underwent more extensive replication than epididymal cells. The mechanism of reduced replication following hypophysectomy differed from that of donor site: hypophysectomy resulted in an increased percentage of cells which underwent 2 or fewer population doublings at the expense of cells capable of more than 2 doublings. However, donor site had little effect specifically on these slowly replicating preadipocytes; rather, perirenal preadipocytes underwent more extensive replication than epididymal cells because of the higher percentage of preadipocytes capable of 13 or more doublings in perirenal fat pads. Hypophysectomy did not result in decreased differentiation of preadipocytes. These observations are in accord with the hypothesis that hypophysectomy reduces fat cell number in maturing rats partly through an effect on preadipocyte replicative capacity. Additionally, it seems that more than one form of preadipocyte exists, the various forms having differing susceptibilities to factors such as pituitary function and anatomic site.
Adipose Tissue↗
[The morphogenic effect of gonadotropic hormones on the Leydig cells of the boar testis. II. Effects of administration of chorionic gonadotropin after hypophysectomy. Effects in vivo and in organ culture].
The longer ago the hypophysectomy has been performed, the more marked is Leydig cell atrophy in the testis. The effects of HCG on cellular morphology have been observed in vivo and in organ culture; qualitative quantitative and ultrastructural aspects were studied. In vivo, the effects of a daily injection of gonadotropin on the testis of 2 boars hypophysectomized 3 1/2 months ago are shown. Markedly atrophied cells are strongly stimulated by HCG during the 15 first days (the cell and nucleus recover nearly to standard size, with the typical histological and ultrastructural appearance with all the cell organelles which characterize a functional steroid cell). Then after 1 1/2 month injection it decreases again to the initial state (very small size cytoplasm strongly reduced with very low organelle content). The number of the Leydig cells is maintained during the first 15 days, then it progressively decreases. The effects of HCG on the testicular tissue of 4 boars were studied in organ culture. Interstitial tissue with a greater or lesser degree of atrophy was examined experimentally (1 month, 3 months and 4 months after hypophysectomy) in order to prove a possible irreversibility of the effects of hypophysectomy. In each case, cell changes were studied according to the duration of the culture. Control cultures without HCG in the medium were set up simultaneously. 1 month and/or 3 months after hypophysectomy, the Leydig cells in culture progressively recover the size and the histological and ultrastructural appearances of a typical Leydig cell. After 16 days of culture, the stimulation is highest, as in vivo. The number of Leydig cells is maintained. From the 17th day stimulation decreases and the cell enters a new atrophy phase. In the anhormonal control medium the atrophy continues as long as the culture is maintained, and the number of Leydig cells decreases. 4 months after hypophysectomy, stimulation in culture is still possible during the first 10 days (proved by the same tests); however the size of the cell remains small compared to the normal; then it atrophies again quickly. In this case the hormone does not maintain the number of the Leydig cells. In the control cultures, slight response of the cell is observed, but this effect is limited and disappears a few days later; the number of the cells rapidly decreases. It has been shown that markedly atrophied Leydig cells can highly be stimulated during the first 2 weeks under the influence of HCG as well in vivo as in organ culture. The lability of the effect is not yet explained. 4 months after hypophysectomy, stimulation is not so effective.
Animals↗
A comparative trial of transsphenoidal hypophysectomy and estrogen suppression with aminoglutethimide in advanced breast cancer.
We compared two treatment regimens, transsphenoidal hypophysectomy and estrogen suppression with aminoglutethimide in women with metastatic breast carcinoma. Three of fourteen patients experienced partial objective tumor regression with a median duration of 4.6 months following hypophysectomy, whereas 10 of 21 women receiving aminoglutethimide responded (2 complete, 8 partial) with a median duration of 11.5 months. Side effects in the medical group were minimal while surgical complications included 2 cases of CSF rhinorrhea, one leading to meningitis and death. In patients receiving aminoglutethimide, urinary free cortisol and plasma dehydroepiandrosterone sulfate fell significantly as did plasma estrone and estradiol. In the hypophysectomy group, anterior-pituitary function testing postoperatively revealed adequate suppression of gonadotropin and prolactin secretion but incomplete inhibition of the ACTH-cortisol axis in 4 of 7 surgical patients studied. Five patients initially treated with hypophysectomy experienced a further reduction of plasma (and urinary) estrone and estradiol levels when given aminoglutethimide. We conclude that estrogen suppression therapy with aminoglutethimide is a feasible alternative to surgical hypophysectomy in providing endocrine suppression and palliation in advanced breast carcinoma.
Adult↗
Transsphenoidal hypophysectomy in breast cancer: evidence for an individual role of pituitary and gonadal hormones in supporting tumor growth.
Transsphenoidal hypophysectomy was performed in 212 consecutive patients with metastatic breast cancer: 11 died within 30 days, two of surgical complications and nine of advanced metastatic disease. Two patients were unevaluable because of inadequate follow-up in one and simultaneous radiation treatment in the other. Of 199 evaluable patients 42% had an objective remission. Duration of remission averaged 18+ months with 10 out of 84 patients still in remission. Presence of estrogen receptors in the tumor significantly predicted response to hypophysectomy. Of 156 patients in whom completeness of hypophysectomy was assessed, 128 were thought to have a complete removal as shown by the fact that their growth hormone and prolactin were undetectable after stimulation with arginine or chlorpromazine, respectively. Of 26 patients in whom TRH test was performed, TSH and prolactin were undetectable in 20. Of 23 patients where autopsy was performed only six had microscopic pituitary tissue remaining. Hypophysectomy induced remission in eight of 15 patients who had previously responded and then relapsed to the antiestrogen Tamoxifen and in four of 17 who had failed. Conversely, antiestrogen therapy induced remission in six of 26 patients who had previously responded to hypophysectomy and in whom serum estrogens were present in small amount. These data indicate that both gonadal and pituitary hormones play a role in the growth of some human breast cancers.
Adult↗
Effects of hypophysectomy on alloxan-diabetic, arteriosclerotic, breeder vs. non-arteriosclerotic, virgin rats.
A single s.c. injection (10 mg/100 g bw of alloxan) was given to nonarteriosclerotic, virgin, Sprague--Dawley rats and to breeder rats with preexisting arteriosclerosis, hyperlipidemia and hyperglycemia. All of the animals promptly developed severe diabetes with ketosis, hyperglycemia, and hyperlipidemia. Insulin therapy was deliberately withheld. Mortality was high. Seven days later one group was subjected to hypophysectomy and 30 days later, all of the animals were autopsied. The diabetes + hypophysectomy animals maintained their body weight better, did not have hypertrophied adrenal glands, showed the least elevation of serum enzymes, e.g., CPK, SGOT, SGPT and LDH, less hyperlipidemia and hyperglycemia and reduced corticosterone production than the animals with untreated severe diabetes. Despite the relative amelioration of metabolic derangements prognostic of cardiovascular degenerative changes, the diabetes + hypophysectomy animals manifested extensive renovascular damage and the breeder rats with pre-existing arteriosclerosis showed definite exacerbation of their arterial disease in response to the severe alloxan diabetes regardless of hypophysectomy. It is suggested that although hypophysectomy may alleviate certain metabolic derangements attributed to growth hormone, ACTH and adrenal steroids, the angiopathic damage proceeds inexorably.
Adrenal Cortex Hormones↗
Further characterization of the effects of hypophysectomy, FSH and estrogen on LH stimulation of testosterone production in Leydig cells isolated from immature rats.
Hypophysectomy of immature rats results after 5 days in a loss of LH responsiveness of Leydig cells. LH responsiveness can be partly maintained by treatment with FSH for 5 days. When estradiol benzoate was administered together with FSH to hypophysectomized rats the maintenance of LH responsiveness was not observed. The loss in LH responsiveness after hypophysectomy in terms of testosterone production could not be explained by either a change in the amount of Leydig cells present in the Leydig cell preparation or to a higher conversion of testosterone. The LH-stimulated cAMP production in cells from hypophysectomized rats was very low compared to cells from intact rats. There was no difference between cAMP production of Leydig cells from untreated, FSH-treated or FSH plus estradiol benzoate treated hypophysectomized rats. During the first 2 days after hypophysectomy LH responsiveness in both untreated and FSH-treated rats showed a comparable decrease. From day 2 after hypophysectomy LH responsiveness remained at a constant level in cells from rats treated with FSH, but declined further in cells from untreated rats. A single injection of estradiol benzoate to hypophysectomized rats treated with FSH counteracted the effect of FSH on LH responsiveness, but only when estradiol was administered at that time after hypophysectomy, when the effect of FSH on LH responsiveness was clear.
Animals↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
The effects of pituitary stalk transection, hypophysectomy and thyroid hormone status on insulin-like growth factor 2-, growth hormone releasing hormone-, and somatostatin mRNA prevalence in rat brain.
We have used in situ hybridization histochemistry to determine the effects of pituitary stalk transection, hypophysectomy and drug-induced changes in thyroid status on mRNA levels encoding insulin-like growth factor 2, somatostatin, and growth hormone-releasing factor in the choroid plexus, hypothalamic periventricular nucleus, and arcuate nucleus, respectively. Pituitary stalk transection and hypophysectomy in Sprague-Dawley rats decreased insulin-like growth factor 2 and somatostatin mRNA and increased growth hormone-releasing factor mRNA. In each case, the effect of hypophysectomy exceeded that of pituitary stalk transection. Treatment with propylthiouracil for 10 days decreased somatostatin mRNA, markedly increased growth hormone-releasing factor mRNA but had no significant effect on insulin-like growth factor 2 mRNA. Treatment with triiodothyronine had no effect on the mRNAs measured. These findings corroborate the clinical observation of abnormal somatic growth in disturbances of thyroid and growth hormone status and provide further evidence of the effects of these metabolic disturbances and of pituitary disconnection and hypophysectomy on insulin-like growth factor 2 mRNA prevalence.
Animals↗