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Changes in fibre types in rat soleus and plantaris muscles following hypophysectomy and compensatory overload.

We investigated whether hypophysectomy could modify the change in muscle fibre types caused by compensatory overload. Male Wistar strain rats were assigned to groups of either normal control (NC), hypophysectomized control (HC), normal compensatory overloaded (NO), or hypophysectomized compensatory overloaded (HO). Compensatory overload was induced by the bilateral removal of the gastrocnemius muscle. Five weeks later, there were losses in the soleus and plantaris muscle weights as a result of hypophysectomy. Compensatory overload increased muscle weights independently of the hypophysectomy. Growth hormone and 3,5,3'-triiodothyronine levels were significantly decreased following hypophysectomy. In the soleus, hypophysectomy increased the percentage of type I fibres at the expense of type IIA fibres. Compensatory overload decreased type IIA fibres under the hypophysectomized condition. In the plantaris, the percentage of type IIC fibres was increased at the expense of both type IIA and IIB fibres following hypophysectomy. The decrease in type IIB fibres cause by compensatory overload was induced irrespective of hypophysectomy. The changes in muscle fibre types in the HO group were equal to the sum of the changes in the HC and NO groups. These results suggest that after a period of 5 weeks hypophysectomy may induced decrease in type IIA and IIB fibres in association with the lack of pituitary and thyroid hormones, and that the hypophysectomy could not modify the change in muscle fibre types caused by compensatory overload.

Aging↗

Plasma profiles of adrenocorticotropic hormone, cortisol, alpha-melanocyte-stimulating hormone, and growth hormone in dogs with pituitary-dependent hyperadrenocorticism before and after hypophysectomy.

The 6-h plasma profiles of adrenocorticotropic hormone (ACTH), cortisol, alpha-melanocyte-stimulating hormone (alpha-MSH), and GH were studied in 17 dogs with pituitary-dependent hyperadrenocorticism (PDH) before and after hypophysectomy. The aim of the study was to investigate the relation between the hormone profile characteristics and recurrence of PDH after surgery. The hormones were secreted in a pulsatile fashion. The basal plasma cortisol concentration and area under the curve (AUC) for cortisol were significantly higher in the PDH cases than in eight controls. The characteristics of the plasma profiles of ACTH and alpha-MSH were not significantly different between the PDH cases and the controls. In the PDH cases, less GH was secreted in pulses than in the controls, but the difference was not significant. The basal plasma cortisol concentration, the AUC for ACTH and cortisol, and the pulse frequency of ACTH and cortisol decreased significantly after hypophysectomy for the group of PDH cases. The basal plasma concentrations of ACTH and alpha-MSH, the AUC for alpha-MSH, and the characteristics of the plasma GH profiles of the PDH cases remained unchanged after hypophysectomy. No pulses of alpha-MSH were observed after hypophysectomy. The co-occurrence between the ACTH and cortisol pulses decreased significantly with hypophysectomy. The postoperative pulse frequency of ACTH was the only characteristic with predictive value for the recurrence of PDH after hypophysectomy. The results of this study demonstrate that ACTH, cortisol, alpha-MSH, and GH are secreted in a pulsatile fashion in dogs with PDH. Hypophysectomy effectively reduces the secretion of ACTH and cortisol. The presence of ACTH pulses after hypophysectomy is a risk factor for the recurrence of hyperadrenocorticism.

Adrenocortical Hyperfunction↗

Characterization of thymic weight and thymic peptide thymosin-beta 4: effects of hypophysectomy, sex, and neonatal sexual differentiation.

An initial experiment was conducted to analyze the effects of hypophysectomy (Days 5-30 post hypophysectomy) on thymic weight and thymosin-beta 4 concentrations. After hypophysectomy, thymic weight and thymosin-beta 4 concentrations decreased with time (5, 10, 15, and 30 days post hypophysectomy) and by 30 days post hypophysectomy were reduced by 50%. Exp. II investigated the effects of early sexual differentiation on thymic weight and thymosin-beta 4 concentrations in pituitary intact and hypophysectomized male, female, nonmasculinized rats (via castration of males at Day 2 or 11 of age and androgenized female (at Day 3 of age) rats. Rats were hypophysectomized at 30 days of age and, at 17 days post hypophysectomy, the thymus gland was dissected and weighed. Serum was collected for thymosin-beta 4 analysis. At 47 days of age, males have a greater thymic weight when compared to females (p less than 0.01) but hypophysectomy eliminated any sex differences and significantly reduced thymic weights (p less than 0.05). Hypophysectomy did produce increased thymosin-beta 4 concentrations across all treatments (p less than 0.01) and is considered to be a combination response of decreased gonadal function via lack of pituitary hormonal stimulation (luteinizing hormone and follicle stimulating hormone) and lack of gonadotrophic effects on the thymus gland and its secretory capacity. Hypophysectomized males and Day-2 castrate males had increased thymosin-beta 4 concentrations when compared to hypophysectomized females and neonatally androgenized females (p less than 0.05). Differences of thymic weights between male and female rats during prepubertal development are probably related more to presence or absence of gonads, gonadal steroids, and response of the thymus to pituitary secretagogues rather than to neonatal sexual differentiation of thymic function and secretion of thymosin-beta 4.

Animals↗

Transsphenoidal hypophysectomy in the clinically normal dog.

Pituitary function and short-term clinical effects after transsphenoidal hypophysectomy were investigated in clinically normal dogs. In study I, 8 dogs were given polyionic fluids IV during the first 12 hours after surgery. In study II, 4 dogs were given polyionic fluids IV and glucocorticoid supplementation for 7 days. Pituitary function was assessed by evaluating basal ACTH concentrations and results of a growth hormone stimulation test before and 1 and 12 weeks after hypophysectomy, an ACTH stimulation test, a thyrotropin-releasing hormone-stimulation test, and a modified water deprivation/vasopressin response test before and 1, 4, 8, and 12 weeks after hypophysectomy. Gross and histologic evaluations of the surgery site, thyroid and adrenal glands, and skin were done at 12 weeks after surgery. Four dogs from study I died within 27 hours after hypophysectomy. Postmortem examinations of these dogs revealed liver and lung congestion compatible with circulatory collapse. None of the dogs in study II died. For the surviving dogs in both studies, diabetes insipidus developed immediately after hypophysectomy and resolved within 2 weeks. Hypernatremia also developed immediately after hypophysectomy and resolved by 1 week. Production of ACTH was evident at 1 and 12 weeks after hypophysectomy in all dogs, and results of ACTH stimulation tests after surgery were not notably different from results obtained before surgery. Results of thyrotropin-releasing hormone stimulation and growth hormone-stimulation tests supported the diagnosis of hypothyroidism and hyposomatotropism attributable to hypophysectomy. Histologic examination revealed thyroid atrophy, epidermal and dermal atrophy, and normal adrenal glands in all dogs and remnants of the hypophysis in 2 dogs from study I.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

Pain relief after hypophysectomy.

Thirteen series of patients who underwent surgical or chemical hypophysectomy for the relief of pain associated with cancer were reviewed. In 10 series, involving 334 patients with breast or prostate cancer, surgical hypophysectomy produced pain relief in 70% of the patients afflicted with either tumor, including some with no evidence of hormone dependence. These results were then compared with the results of chemical hypophysectomy. This procedure was performed in 3 series involving 533 patients, of whom 24% had cancer other than breast or prostate. Chemical hypophysectomy produced pain relief in over 75% of the patients, regardless of tumor type or hormonal dependence. The possible role of the pituitary, the hypothalamus, and endogenous opiates in mediating the pain relief associated with hypophysectomy was examined. The mechanism by which pain relief is achieved remains unclear, but there is significant evidence that this relief is not related directly to the expected fall in the levels of known pituitary hormones. Evidence is provided that pain relief is the result of a hypothalamic pain-suppressing capability triggered by hypophysectomy. On the basis of both clinical data and the mechanism of action, we conclude that surgical and chemical hypophysectomy are fundamentally similar procedures.

Breast Neoplasms↗

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↗

Transsphenoidal hypophysectomy for treatment of pituitary-dependent hyperadrenocorticism in 7 cats.

OBJECTIVE: Evaluation of microsurgical transsphenoidal hypophysectomy for the treatment of pituitary-dependent hyperadrenocorticism (PDH) in cats. STUDY DESIGN: Prospective clinical study. ANIMALS OR SAMPLE POPULATION: Seven cats with PDH. METHODS: Urinary cortisol/creatinine ratios, pituitary-adrenocortical function tests, and computed tomography (CT) were performed on 7 cats that presented with a provisional diagnosis of hyperadrenocorticism. All cats underwent microsurgical transsphenoidal hypophysectomy with histologic examination of the excised specimen. Follow-up consisted of clinical evaluation, repeat adrenocortical function testing, and CT. RESULTS: Four cats had concurrent diabetes mellitus. In all cats, the urinary cortisol/creatinine (C/C) ratios were elevated. The dexamethasone screening test showed that 2 cats did not meet the criterion for hyperadrenocorticism. The response of the cats' plasma concentrations of cortisol and adrenocorticotrophic hormone to a high dose of dexamethasone varied from very sensitive to completely dexamethasone resistant. Basal plasma alpha-melanocyte-stimulating hormone concentrations were elevated in 2 cats with a pars intermedia adenoma and in 3 cats with an adenoma that originated from the anterior lobe. Preoperative CT enabled accurate assessment of pituitary size (5 nonenlarged pituitaries with a height <4 mm and 2 enlarged pituitaries with a height >5 mm) and localization relative to intraoperative anatomic landmarks. Two cats died within 4 weeks after surgery of a nonrelated disease. In the remaining 5 cats, the hyperadrenocorticism went into both clinical and biochemical remission. Hyperadrenocorticism recurred in 1 cat after 19 months, but no other therapy was given and the cat died at home 28 months after surgery. CT evaluation of this cat had identified pituitary remnants 6 weeks after surgery. The main postoperative complications were oronasal fistula (1 cat), complete dehiscence of the soft palate (1 cat), and transient reduction of tear production (1 cat). One cat died at 6 months (undefined anemia), and another cat at 8 months (recurrent nose and middle ear infection secondary to soft palate dehiscence) after surgery. In the surviving 2 cats, the remission periods at the time of writing were 46 and 15 months. In the 2 cats with sufficient follow-up time, the concurrent diabetes mellitus disappeared, ie, insulin treatment could be discontinued at 4 weeks and 5 months after hypophysectomy. In all 7 cats, the histologic diagnosis was pituitary adenoma. CONCLUSIONS: Microsurgical transsphenoidal hypophysectomy is an effective method of treatment for feline PDH in specialized veterinary institutions having access to advanced pituitary imaging techniques. Concurrent diabetes mellitus is usually reversible after hypophysectomy. Thorough presurgical screening for coexisting diseases is imperative. CLINICAL RELEVANCE: PDH in cats can be effectively treated by hypophysectomy. The neurosurgeon performing hypophysectomy must master a learning curve and must be familiar with the most frequent complications of the operation to treat them immediately and effectively. Urinary C/C ratios are sensitive indicators for the assessment of remission and recurrence of hyperadrenocorticism.

Adenocarcinoma↗

[Hypophysectomy in metastasing carcinoma of the breast (author's transl)].

As result of a poll, the opinion of 50 Neurosurgical Departments in the Federal Republic of Germany relating to the importance of hypophysectomy in the therapy of metastatic carcinoma of the breast was obtained. Four of 32 replies prefer a regular hypophysectomy and 11 departments do the hypophysectomy only in exceptional cases. In 17 clinics this operation is not used. It should be emphasized, that a quarter of those neurosurgeons, who took part in our inquiry, had already given up hypophysectomy some years ago. About 50% of the surgeons talk about positive effects on metastatic carcinomas. The hormonal dependence of disseminated cancers is the only condition, which has to be presumed. Implantation of radioisotopes and trans-sphenoidal hypophysectomy are mentioned as the main operative techniques. The indications for hypophysectomy for metastatic carcinoma of the breast are discussed in the light of the recent literature. If one considers the possibilities of radiotherapy and chemotherapy, hypophysectomy can still be of considerable value as a palliative measure in hormone-dependent tumours with bone metastases, provided that the cases are carefully selected.

Bone Neoplasms↗

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↗

The response of magnocellular neurons of the hypothalamo-neurohyphyseal system to hypophysectomy, nitric oxide synthase expression as well as survival and regeneration in developing vs. adult rats.

This study examined the age-related changes in nitric oxide synthase immunoreactivity (NOS-IR), survival and regeneration of magnocellular neurons in the hypothalamo-neurohypophyseal system (HNS) in rats following hypophysectomy. In adult animal, hypophysectomy induced a significant increase in NOS-IR in the supraoptic (SON), paraventricular nuclei (PVN) and median eminence (ME) by 3 days post-lesion. NOS sustained an increased level until 2 weeks after hypophysectomy and then returned to normal control level. In contrast, at postnatal day 7 (PN7), no obvious increase in NOS-IR was observed in the SON, PVN and ME following the injury compared with age-matched controls. At PN14, the same injury induced an increase in NOS-IR in SON, PVN and ME but the increase was more transient with peak NOS-IR at 3 days and returning to the corresponding control level at 1 week after hypophysectomy. In contrast to a striking age-dependent alteration in NOS-IR in the SON and PVN, hypophysectomy induced substantial degeneration of arginine vasopressin (AVP) and oxytocin (OT) neurons in the SON and PVN in both immature and adult rats and there was no obvious difference in neuronal survival after the same injury among these three groups of different ages by quantitative analysis. Following hypophysectomy, a large number of fibers were observed in the contact zone of the median eminence and the adjacent lumen of the third cerebral ventricle (V3) in adult rats, whereas few fibers could be found in the lumen of the V3 in the immature rats after the same injury. Relationships between NOS induction and magnocellular neuronal survival and regeneration were discussed.

Age Factors↗

Immunohistochemical distribution of isoenzymes of glutathione transferase in adult rat adrenal gland before and after hypophysectomy.

The distribution of glutathione transferase subunits 1, 2, 3, 4, 7 and 8 in the different cells of the female and male rat adrenal and the effects of hypophysectomy on these isoenzymes were studied using immunohistochemical methods. All these glutathione transferase subunits, with the exception of subunit 1, were present in the adrenal. Each subunit showed, however, its own characteristic distribution pattern. After hypophysectomy, increased staining for these isoenzymes was generally observed, and this effect was also cell-specific. Staining for subunit 2 increased in intensity in the zona fasciculata and reticularis after hypophysectomy, whereas a decrease was observed in the zona glomerulosa. Staining for subunit 8 was increased in the borderline between the capsule and zona glomerulosa, as well as in medullary chromaffin cells after hypophysectomy. The Mu subunits 3 and 4 increased markedly in fascicular and reticular cells after hypophysectomy and staining for subunit 3 was also increased in the medullary cells. A slight, but more general, increase was observed for subunit 7. We conclude from these experiments that the increases in glutathione transferase subunits observed in the rat adrenal after hypophysectomy are due to increased protein synthesis and/or increased protein stability and not to a selective destruction of cells lacking, or with low levels of, the isoenzymes.

Adrenal Glands↗

Flow cytometric quantification of rat spermatogenic cells after hypophysectomy and gonadotropin treatment.

DNA flow cytometry was evaluated as a tool to analyze stage-specific changes that occur in absolute cell numbers in the testes. Hypophysectomy was selected as a model system for perturbing testicular cell types, since the cytological sequelae of this treatment post-hypophysectomy in the rat are well documented in the literature. Rat spermatogenic cells in stages II-V, VII, and IX-XIII of the seminiferous epithelial cycle (as defined by Leblond and Clermont, 1952) were quantified in numbers per standard length of seminiferous tubule by DNA flow cytometry after hypophysectomy and subsequent gonadotropin treatment. In agreement with previous histological studies, we found that acrosome- and maturation-phase spermatids disappeared from the seminiferous epithelium after 17 days post-hypophysectomy, whereas meiosis and early spermiogenesis continued at least 164 days. The number of meiotic cells and round spermatids gradually decreased after hypophysectomy. Changes were observed as early as Day 6 post-hypophysectomy. Treatment with human chorionic gonadotropin (hCG) alone maintained most cell numbers within normal limits, and follicle-stimulating hormone (FSH) was needed in addition to hCG to maintain the normal number of cells with the amount of DNA contained in primary spermatocytes and spermatogonia in G2/M-phase (4C) in stages IX-XIII and elongated spermatids (1C') in stages II-V of the epithelial cycle. The absolute numbers of spermatogenic cells at different phases of maturation provide a useful reference for quantitative studies of spermatogenesis. Pathological changes in the seminiferous epithelium can be detected and quantified by DNA flow cytometry.

Acrosome↗

Results of transsphenoidal hypophysectomy in 52 dogs with pituitary-dependent hyperadrenocorticism.

OBJECTIVE: To evaluate microsurgical transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism (PDH). STUDY DESIGN: Prospective study to evaluate the results (survival and disease-free interval, remission, recurrence) and complications of microsurgical transsphenoidal hypophysectomy by clinical follow-up, computed tomography (CT), and urinary corticoid-to-creatinine (C/C) ratios in dogs with PDH. The effect of surgical experience was investigated by comparing results of hypophysectomy cases 1 through 26 and 27 through 52. ANIMALS OR SAMPLE POPULATION: 52 dogs with PDH. RESULTS: Preoperative CT enabled accurate assessment of pituitary size (24 nonenlarged and 28 enlarged) and localization relative to intraoperative anatomic landmarks. Treatment failures included procedure-related mortalities (five dogs) and incomplete hypophysectomies (four dogs). The 1-year estimated survival rate was 84% (95% confidence interval [CI], 71% to 92%). The 2-year estimated survival rate was 80% (95% CI, 65% to 90%). In 43 dogs, the hyperadrenocorticism went into remission. Hyperadrenocorticism recurred in five dogs. The 1-year estimated relapse-free fraction was 92% (95% CI, 76% to 97%). The main complications were transient, mild, postoperative hypernatremia; transient reduction or cessation of tear production (25 eyes in 18 dogs); permanent (five dogs) or prolonged (nine dogs) diabetes insipidus; and secondary hypothyroidism. Normal tear production had resumed in all but one case after a median period of 10 weeks. In the second case series (27 through 52), the hospitalization period was shorter, the number of dry eyes fewer, the survival fraction greater, and the postoperative mortality lower than in the first series. In 15 dogs in which remission was obtained, postoperative CT images suggested the presence of small pituitary remnants; in 1 of these, hyperadrenocorticism recurred. In 46 dogs, the histological diagnosis was pituitary adenoma. CONCLUSIONS: Microsurgical transsphenoidal hypophysectomy in dogs with PDH is an effective method of treatment in specialized veterinary institutions having access to advanced pituitary imaging techniques. Postoperative CT findings do not correlate well with remission or subsequent recurrence of hyperadrenocorticism. CLINICAL RELEVANCE: The neurosurgeon performing hypophysectomies must master a learning curve and must be familiar with the most frequent complications of the operation to recognize them as early as possible and to treat them immediately and effectively. Urinary C/C ratios are sensitive indicators for the assessment of remission and recurrence of hyperadrenocorticism.

Adrenocortical Hyperfunction↗

Structural manifestations of the rat Sertoli cell to hypophysectomy: a correlative morphometric and endocrine study.

Although the Sertoli cell is a key cell mediating the actions of FSH- and LH-stimulated testosterone (T) in the testis, there is little information to indicate how this cell responds structurally to hormonal insufficiency. The present study used morphometric techniques to study the structural manifestations of the Sertoli cell in adult rats hypophysectomized for 6 and 28 days. Six days posthypophysectomy, a period when germ cell degeneration is first evident, tubular diameter and length, testis weights, volume of the interstitium, and volume of most parameters that comprise the interstitium (except blood vessels) showed significant regressive features. However, virtually no parameter relating to the volume and surface area of the Sertoli cell or its subcellular components was significantly reduced compared with that in the normal animal. Thus, at a time when germ cell degeneration is seen in the testis, the Sertoli cell showed no significant structural response to the changing endocrine status of the animal. In contrast, 28 days after hypophysectomy, virtually all parameters relating to the Sertoli cell and its organelles were significantly decreased compared with those in normal animals. Plasma and tissue testosterone, PRL, and FSH showed a very significant decrease 6 days after hypophysectomy compared with intact animals, but at 28 days there was no further significant decrease in the levels of these hormones. There was no correlation of most organelle volumes and surface areas with endocrine parameters. The size of the Sertoli cell showed positive and significant correlations with the volumes and surface areas of all of its cytoplasmic organelles, except the lipid volume. Short term hypophysectomy resulted in no significant change in either the concentration (femtomoles per mg protein) or the content (femtomoles per testis) of FSH receptors, nor was there a significant change in the number of FSH receptors per cell. However, 28 days after hypophysectomy only the content, not the concentration, of FSH receptors decreased significantly along with a decrease in the number of FSH receptors per cell. Although the marked degenerative changes that are seen in the testis 6 days after hypophysectomy parallel endocrine decline, the Sertoli cell responded slowly from a structural standpoint compared with the Leydig cell. After long term hypophysectomy, significant morphometric changes were observed in all of its structural parameters.

Animals↗

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↗

Residual pituitary function after transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism.

Pituitary function was assessed before and after transsphenoidal hypophysectomy in 39 dogs with pituitary-dependent hyperadrenocorticism (PDH). Anterior pituitary function was investigated using combined administration of four hypophysiotropic releasing hormones (corticotropin-releasing hormone (CRH), GHRH, GnRH, and TRH) with measurements of ACTH, cortisol, GH, LH, prolactin (PRL), and TSH Pars intermedia function was assessed by measurements of basal plasma alpha-MSH concentrations and adrenocortical function by baseline urinary corticoid/creatinine ratios. At eight weeks after hypophysectomy basal plasma ACTH, cortisol, GH, LH, PRL, and TSH concentrations were significantly lower than before surgery. In seven dogs with elevated alpha-MSH concentrations, the values returned to the normal level after surgery. In the combined anterior pituitary function test there were no plasma GH, LH, PRL, and TSH responses to stimulation, whereas plasma ACTH and cortisol responses were small but significant. Remission of hyperadrenocorticism was obtained in 35 dogs and recurrences occurred in 3 of these within 16 months postoperatively. At 8 weeks after hypophysectomy, these 3 dogs were not discernible, with respect to residual pituitary and adrenocortical function, from the 32 dogs with persisting remission. Urinary corticoid/creatinine ratios in the latter group of dogs did not increase during 22 months after hypophysectomy. In contrast to the presurgical findings, at 8 weeks after hypophysectomy there were significant positive correlations between baseline urinary corticoid/creatinine ratios and basal levels and responses for ACTH, indicating return to normal function of the pituitary-adrenocortical axis. It is concluded that among the adenohypophyseal cells present in the sella turcica after hypophysectomy, the corticotropes have a distinct behavior. Much more so than the other cell types, the unaffected corticotropes tend to remain functional, or a repressed reserve fraction of corticotropes may become functional. This may be due to the removal of the hypothalamic influence of a postulated corticotropin-release inhibiting factor or a diminished inhibitory influence of a postulated paracrine factor. The corticotropes may maintain normocorticism, but may also lead to mild recurrence after relatively long periods of remission.

Adrenocortical Hyperfunction↗

Efficacy of transsphenoidal hypophysectomy in treatment of dogs with pituitary-dependent hyperadrenocorticism.

The long-term survival, disease-free fractions, and the complications of hypophysectomy in 150 dogs with pituitary-dependent hyperadrenocorticism (PDH) were examined in a prospective study. Long-term survival and disease-free fractions in relation to pituitary size were analyzed by the Kaplan-Meijer estimate procedure. The 1-, 2-, 3-, and 4-year estimated survival rates were 84% (95% confidence interval [CI], 76-89%), 76% (67-83%), 72% (62-79%), and 68% (55-77%), respectively. Treatment failures included procedure-related mortalities (12 dogs) and incomplete hypophysectomies (9 dogs). The 1-, 2-, 3-, and 4-year estimated relapse-free fractions were 88% (CI: 80-93%), 75% (64-83%), 66% (54-76%), and 58% (45-70%), respectively. Postoperative reduction of tear production (58 eyes in 47 dogs) was often reversible but remained low until death in 11 eyes of 10 dogs. Central diabetes insipidus (CDI) occurred more frequently (62%) in dogs with enlarged pituitaries than in dogs with nonenlarged pituitaries (44%). Survival and disease-free fractions after hypophysectomy were markedly higher in dogs with nonenlarged pituitaries than in dogs with enlarged pituitaries. Transsphenoidal hypophysectomy is an effective treatment for PDH in dogs. The survival and disease-free fractions after hypophysectomy decrease and the incidence of CDI increases with increasing pituitary size. Therefore, early diagnosis of PDH is important and transsphenoidal hypophysectomy is expected to have the best outcome when used as primary treatment for dogs with nonenlarged or moderately enlarged pituitaries.

Adrenocortical Hyperfunction↗