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Hormonal influences on the level of testicular androgen binding activity: effect of FSH following hypophysectomy.

Concentrations of high affinity (Ka equals 5.5 plus or minus 0.83 times 10-8M-1) androgen binding activity in carbonextracted rat testicular supernatants have been determined by Scatchard plot analysis under a variety of hormonal situations: (a) 0-90 days following hypophysectomy; (b) 0-60 days of daily injection of NIH-FSH-P1 (150 mug) beginning 1 day after hypophysectomy; and (c) 0-60 days of daily FSH treatment beginning 30 days after hypophysectomy. The high affinity binding component declined from 0.32 pmoles/mg protein intact adults to 0.28, 0.17, and less than 0.08 (limit of detectability) pmoles/mg protein at 11, 16 and 31 days, respectively. FSH treatment beginning immediately after surgery slowed this decline, giving values of 0.30, 0.17, and 0.12 pmoles/mg protein after 11, 29, and 54 days of treatment, respectively. Expressed as pmoles per testis this represented 96, 61, and 40% of the intact control level. Similar effects on the level of androgen binding protein (Rf 0.54) were measured by steady-state polyacrylamide gel electrophoresis (PAGE). The concentration in both testis and epididymis declined gradually to nondetectable levels by 30 days after surgery. FSH treatment for 11, 29, and 54 days, respectively, resulted in 0.37, 0.38, and 0.03 pmoles of sites/mg protein in testis compared to 0.34 in intact controls and 5.7, 2.6, and 0.2 pmoles/mg protein in epididymis compared to 2.8 in intact controls. Doses of 80, 150, and 300 mug FSH/rat/day for 3 days beginning 30 days after hypophysectomy when postmeiotic elements of the germinal epithelium had degenerated caused graded increases in both testicular and epididymal levels of androgen binding protein. Prolonged FSH treatment (150 mug) under these conditions resulted in an increase in binding activity to a level of 0.12, 0.19, 0.17, and 0.20 pmoles/mg protein after 3, 11, 25, and 56 days of treatment. On a per testis basis this represented less than 20% of intact control levels. PAGE estimates were comparable except at the long treatment intervals. These results indicate that FSH treatment influences the level of androgen binding protein in adult testis and epididymis. This may reflect a direct influence on synthesis, degradation, and transport and/or indirect effects on general maintenance and responsiveness of the pertinent cell types.

Animals↗

The effect of hypophysectomy and prolactin therapy on water balance of the brown trout Salmo trutta.

A technique for the hypophysectomy of the brown trout is described which might be applicable to other salmonids. Hypophysectomy produced a decrease in water turnover which was corrected by prolactin therapy. Hypophysectomy resulted in a decrease in the next flux of osmotic water. Both osmotic and diffusional water permeabilities were evenly decreased after hypophysectomy, such that the ratio of the osmotic and diffusional permeability coefficients (Pos/Pd) retained a value of approximately unity. The data suggest that calcium and prolactin have opposing actions on water balance and that their modes of action are likely to separate.

Animals↗

Functional and morphological changes in the hypothalamus-pituitary posterior lobe system after hypophysectomy in the dog.

Acute diabetes insipidus-like symptoms have been reported as a complication after hypophysectomy in dogs. These symptoms are believed to be the consequence of deficiency of arginine vasopressin (AVP) secretion. The symptoms spontaneously resolve within 2 weeks, but the mechanism is unclear. In the present study, AVP secretion related to increases in Na+ concentration and serum osmotic pressure was measured, and immunohistochemical analysis in the paraventricular and supraoptic nuclei was performed after hypophysectomy in normal dog. In the hypertonic saline test, the plasma AVP concentration slightly increased in hypophysectomized dogs, although the increase was markedly smaller than that in normal dogs. An immunohistochemical study of the hypothalamus nucleus revealed that, AVP-positive cells tended to decrease after hypophysectomy. It suggests that excision of the posterior lobe by surgery injured the axon of magnocellular neuron in the hypothalamus. A decrease in the function and the number of AVP-producing and -secreting magnocellular neurons after hypophysectomy, suggests that the clinical improvement of postoperative diabetes insipidus-like symptoms may not be related to the recovery of AVP secretion.

Animals↗

Effect of hypophysectomy and growth hormone administration on somatostatin and gastrin content in the stomach of rats.

The effect of hypophysectomy and bovine growth hormone (GH) administration on somatostatin (SRIF) content as well as gastrin content in the rat stomach was investigated. SRIF content was determined by a specific radioimmunoassay. The total SRIF content in the stomach had decreased 4 weeks after hypophysectomy but was restored significantly in those rats which were subjected to bovine GH administration for 7 days after hypophysectomy. Furthermore, in control rats, an increase in SRIF content in the stomach was observed after 7 days of GH administration. Similar changes in total content of gastrin were observed after hypophysectomy and bovine GH administration, although these changes were not significant. These results indicate that GH may influence gastric function through changes in SRIF and gastrin content in the stomach.

Animals↗

The influence of hypophysectomy on NSILA concentrations in the dog: evidence for partially pituitary-independent regulation.

Non-suppressible insulin-like activity (NSILA) was determined in 5 dogs before and after hypophysectomy. All NSILA determinations were carried out on serum samples after acidic Sephadex G-50 chromatography by two different assay systems, i.e. a bioassay and a protein binding assay. The levels of NSILA decreased significantly after hypophysectomy and returned to near normal levels after 2 weeks. T3-, T4- and cortisol levels were drastically reduced during the entire period of the experiment. Several GH determinations after hypophysectomy revealed very low levels. Insulin-induced hypoglycaemia failed to provoke a rise of GH levels as late as 4 months after hypophysectomy. These findings indicate that: 1) The pituitary gland cannot be the site of synthesis of NSILA. 2) NSILA concentrations in the dog are maintained at a near normal level in the presence of very low growth hormone and thyroid hormone concentrations, so that these latter hormones do not appear to be the only regulatory factors concerned in NSILA synthesis.

Animals↗

Follicular growth and regression during the 8 days after hypophysectomy in sheep.

Ewes were hypophysectomized on Day 0 and ovariectomized 1, 2, 4 or 8 days later. There was no effect of hypophysectomy on the overall population of follicles greater than 0.8 mm in diameter during the time studied. However, the growth of healthy follicles greater than 2 mm in diameter was prevented by Day 2. Turnover of follicles was very active in the ovaries of hypophysectomized ewes as shown by peaks in the proportion of follicles in early atresia at Day 4 and in advanced atresia at Days 1 and 8. By Day 8, most of the measures of the population of follicles 0.8 to 2 mm in diameter were back to the values of Day 0 ewes. The mitotic index of the granulosa cells of the healthy follicles exhibited a similar pattern with a nadir at Day 2 followed by a return at Days 4 and 8 to values similar to Day 0 ewes. Ink-marked preovulatory follicles underwent a steady decrease in their histological size after hypophysectomy and this was associated with time-related changes in the health status of these follicles. By Day 1, 4 out of 7 follicles were still healthy while at Days 2, 4 and 8, all follicles were in advanced, late and collapsing atresia respectively. There was no evidence of an ability of PMSG (1000 i.u.) to rescue large follicles in advanced atresia (48 h after hypophysectomy). Furthermore, at 24 h after hypophysectomy, only 2 out of 5 follicles were maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Early hypophysectomy of sheep fetuses: effects on growth, placental steroidogenesis and prostaglandin production.

The factors involved in the control of steroid secretion from the ovine placenta and in fetal growth are as yet unclear. We hypothesized that factors derived from the fetal pituitary may play a role in the production and release of placental steroids and in growth of the fetus, and have investigated the effects of fetal hypophysectomy performed between day 70 and day 79 of gestation (term = 147 days) on systemic concentrations of hormones derived from the placenta, and on fetal growth. Maternal peripheral progesterone, placental lactogen and uterine vein progesterone increased significantly from day 90 in all ewes. Peripheral concentrations of prostaglandin E2 and peripheral and uterine vein oestrone sulfate increased significantly in the control group but not in the fetal hypophysectomy group. Uterine vein prostaglandin E2 increased significantly after day 95 in the control group and after day 105 in the fetal hypophysectomy group. Early fetal hypophysectomy caused marked growth retardation. The weights of the brain, kidneys and liver of hypophysectomized fetuses were the same as those of controls suggesting that their growth is not under pituitary control. In contrast, the weights of heart and lungs were reduced in proportion to body weight, suggesting that heart, lung and carcass growth were under pituitary control. Our data indicate that the fetal pituitary influences the control of placental steroid and prostaglandin E2 biosynthesis after day 90 of gestation in sheep, but that output of other hormones such as placental lactogen is independent of pituitary control, and may determine organ-specific growth parameters that are unaffected by removal of the fetal pituitary.

Animals↗

Morphological changes of somatostatin neurons in the suprachiasmatic nucleus by hypophysectomy of the rat.

After hypophysectomy, behavioral circadian rhythmicities in the rat became indistinct and phase shift was observed. Therefore, it was thought that the suprachiasmatic nucleus (SCN), which is the circadian oscillator in mammals, was affected by hypophysectomy. We investigated the effects of hypophysectomy on SCN neurons using immunohistochemical staining. Wistar-Imamichi strain male rats were hypophysectomized at 60 days old. Their brains were fixed by acrolein perfusion at 10, 30 and 60 days after the operation, and then vasopressin (AVP)-, vasoactive intestinal polypeptide (VIP)- and somatostatin (SRIH)- neurons in the SCN were stained immunohistochemically. Ten days after the operation, SRIH-neurons were not found in the SCN. At 30 and 60 days after the operation, a few SRIH-positive cell bodies were recognized. In contrast, AVP- and VIP- neurons did not change in morphology in comparison with normal rats. These results suggest that hypophysectomy produces an essential change in SRIH neurons in the SCN, and that such change is responsible for the abnormal behavioral rhythms.

Animals↗

Alteration in the expression of genes for cholesterol side-chain cleavage enzyme and 21-hydroxylase by hypophysectomy and ACTH administration in the rat adrenal.

The changes in steady-state levels of mRNA for cholesterol side-chain cleavage cytochrome P-450 (P-450scc) and steroid 21-hydroxylase cytochrome P-450 (P-450c21) caused by hypophysectomy and ACTH treatment were determined in rat adrenals. Hypophysectomy caused marked decreases in adrenal weight and total RNA per gland. Administration of ACTH resulted in increases in adrenal weight and total RNA. A significant correlation between the amount of RNA and adrenal weight was observed. Both P-450scc and P-450c21 mRNAs were decreased by hypophysectomy and increased by ACTH treatment. P-450scc mRNA decreased to 20% and P-450c21 mRNA to 76% of control values 1 day after hypophysectomy. ACTH caused a significant increase in P-450scc mRNA after 3 h. However, a significant increase in P-450c21 mRNA was observed 12 h after administration of ACTH. These results are concordant with previous studies in vitro utilizing cultured adrenocortical cells. Moreover, the induction of steady-state levels of P-450scc mRNA was faster than that observed by other investigators in studies in vitro. These results may indicate that integrity of the adrenal gland in vivo is important for the action of ACTH.

Adrenal Glands↗

Relatively greater increase of oxytocin than vasopressin in the supraoptic nucleus of rats after hypophysectomy.

The vasopressor and milk ejection activities were estimated in the supraoptic region of the hypothalamus of rats which had been hypophysectomized 30 min, 4 and 8 days earlier. Both pressor and milk ejection activities were significantly greater 4 days after hypophysectomy than those in sham-operated control rats. Eight days after hypophysectomy, pressor activity decreased below control values but milk ejection activity was still significantly raised. Increased biological activity after hypophysectomy is thus associated with the previously observed increase in neurosecretory material within the supraoptic nucleus so these results provide additional evidence that neurosecretory material represents stored hormone. Milk ejection activity increased relatively more than pressor activity which supports the suggestion that the final stage in the formation of neurohypophysial hormones occurs as they pass from the hypothalamus to the neural lobe. If this final maturation normally occurs more slowly for oxytocin than for vasopressin, the obstruction to the flow of hormones down the neural stalk caused by hypophysectomy would result in a greater increase in milk ejection than pressor activity.

Animals↗

Effects of hypophysectomy and metyrapone on the catecholamine content and volumes of adrenaline- and noradrenaline-storing cells in the rat adrenal medulla.

Using morphometric analysis and high-pressure liquid chromatography with electrochemical detection of catecholamines the volumes of adrenaline-storing (A) and noradrenaline-storing (NA) cells and the adrenaline and noradrenaline contents of adrenal glands of normal and age-matched hypophysectomized rats were determined and compared. Some hypophysectomized rats were also administered 150 mg metyrapone/kg daily for a 4-week period. Hypophysectomy resulted in an increase in noradrenaline storage in adrenal glands. This was more marked in hypophysectomized animals not treated with metyrapone even though the combination of metyrapone and hypophysectomy resulted in a reduction of blood corticosterone concentration to only approximately 6% normal. There was no evidence of a change in proportion of A and NA cells in the adrenal medulla of hypophysectomized rats or hypophysectomized animals treated with metyrapone and it is concluded that the changes in amine concentrations and proportions observed reflect an increase in the storage of noradrenaline in A cells as a consequence of less efficient methylation of noradrenaline after hypophysectomy. The findings also showed that the left adrenal gland and medulla was usually slightly larger and had a greater catecholamine content and slightly higher proportion of NA cells than the right adrenal gland. During the period of the experiment (animals aged 6-15 weeks) there was an increase in the concentration of both adrenaline and noradrenaline in the normal adrenal glands. In normal Sprague-Dawley rats weighing 140 and 400 g the adrenal medulla accounted for some 5% of adrenal volume; this increased to 13% after hypophysectomy; A and NA cells together accounted for 50-60% of the volume of adrenal medulla.

Adrenal Medulla↗

Effects of hypophysectomy and human chorionic gonadotrophin on Leydig cell function in mature rats.

The biochemical activities involved in the maintenance of Leydig cell functions, and the effects of hypophysectomy and human chorionic gonadotrophin (hCG) on these functions are largely unknown. In the present study, adult hypophysectomized rats were used as a model to determine the effects of these treatments on a number of biochemical and morphological parameters. After 33 days of hypophysectomy, the morphology of the Leydig cells had been drastically altered. In addition, alpha-naphthol and beta-naphthol esterase activity as well as the steroidogenic capacity of the Leydig cells were greatly reduced at this time. In contrast, the level of sterol carrier protein 2 (SCP2), a Leydig cell-specific protein, was affected by hypophysectomy much less than the other parameters measured. Two daily injections of hCG to rats hypophysectomized for 31 days resulted in no change in the morphology of the Leydig cells, or in their proliferative activity. Non-specific esterase activities were also unaffected by 2 days of treatment with hCG. However, two injections of hCG to rats hypophysectomized for 31 days resulted in nearly complete restoration of steroidogenic capacity, and a 3.5-fold increase in the level of SCP2. These findings indicate that hypophysectomy results in significant morphological and biochemical changes in Leydig cells, and that hCG is capable of restoring some of these capacities within a short time.

3-Hydroxysteroid Dehydrogenases↗

The effect of hypophysectomy on inhibin production by adult rat ovaries: changes in ovarian inhibin gene expression and serum inhibin.

We have investigated the effect of hypophysectomy on adult rat ovarian inhibin alpha- and beta A-subunit mRNA, serum inhibin, and circulating gonadotrophin levels. Immediate declines in ovarian inhibin gene expression and serum inhibin were observed following hypophysectomy, with a nadir on day 4. However, inhibin synthesis determined by these parameters was still apparent at 16 days post-hypophysectomy. Gonadotropin levels were suppressed following hypophysectomy and the fall in inhibin production was highly correlated with disappearance of FSH from the circulation. This study demonstrates that removal of pituitary gonadotropin stimulation results in diminished ovarian inhibin synthesis and provides further evidence indicating that FSH stimulates granulosa cell inhibin synthesis by enhancing inhibin gene transcription.

Animals↗

Transsphenoidal hypophysectomy for disseminated carcinoma of the prostate gland. Results in 53 patients.

Transsphenoidal microsurgical hypophysectomy was performed in 53 men with disseminated carcinoma (Stage IV) of the prostate gland. The mean age was 64.8 years. Forty-three of the 53 men had severe pain due to their disease. Significant pain relief was obtained following hypophysectomy, usually within 24 hours, in 39 (91%) of these 43 patients. Objective remission occurred in 16 (36%) of 45 patients in whom the follow-up review was adequate to make this decision. Although dramatic, pain relief was not permanent in every patient. Four patients died in the early postoperative period, and in one, death was directly related to the operative procedure. Significant complications included partial diabetes insipidus in 40 cases (75.5%), and cerebrospinal fluid leaks in six (11.3%). The authors conclude that hypophysectomy is an appropriate operation in patients with disseminated carcinoma of the prostate gland, particularly when pain is a significant feature of the illness. Further, the transsphenoidal microsurgical approach appears to be the operative procedure of choice for performing hypophysectomy.

Aged↗

Sphenoid sinus mucocele: a rare complication of transsphenoidal hypophysectomy.

Only seven cases of a sphenoid mucocele occurring after transsphenoidal hypophysectomy have been previously reported in the world literature. In this article, we report a new case, which occurred in a 67-year-old man. The sphenoid sinus mucocele developed 12 years following transsphenoidal hypophysectomy and adjunctive radiotherapy. The patient was successfully managed with incision and drainage. Although transsphenoidal hypophysectomy is a common operation, this particular complication appears to be rare or at least under-reported. Sphenoid sinus mucocele deserves consideration in the differential diagnosis of a sphenoidal parasellar mass in a patient who has undergone an earlier transsphenoidal hypophysectomy.

Aged↗

[Indications for total hypophysectomy in Cushing's disease].

OBJECTIVE: Transsphenoidal selective adenomectomy is the treatment of choice for Cushing's disease. In some patients, magnetic resonance imaging (MRI) fails to detect small pituitary ACTH-secreting adenomas. Total hypophysectomy can be performed when MRI appears normal. The aim of this paper is to study results and complications after total hypophysectomy for Cushing's disease. METHODS: Between July 1988 and May 1999, 49 patients underwent transsphenoidal surgery for Cushing's disease at our institution. The criteria for inclusion in this study were clinical and biochemical studies strongly suggestive of Cushing's disease with normal MRI. Total hypophysectomy was performed in 7 patients who fulfilled these criteria. Their results were analyzed retrospectively. RESULTS: The average age of the patients was 43 years; there were 7 women. Five adrenocorticotrophic hormone-secreting adenomas were proven histologically. Complications occurred in 6 patients (cerebrospinal fluid fistulas in 6 patients, loss of vision in 1 patient, meningitis in 5 patients, anterior pituitary insufficiency in 5 patients, diabetes insipidus in 5 patients). Six patients had sustained remission 36 months after surgery. CONCLUSION: Total hypophysectomy can be perform ed for Cushing's disease with normal MRI. Complications occurs frequently, especially cerebrospinal fluid fistulas. Inferior petrosal sinus sampling can be helpful in localizing the adenoma allowing hemihypophysectomy and thus reduced morbidity.

Adenoma↗

Morphometrical analysis of the short-term effects of hypophysectomy and food restriction on skeletal muscle fibers in relation to growth and aging changes in the rat.

Muscle fiber growth is impaired by lack of hormonal influence. In the case of the gastrocnemius muscle of the male Wistar rat, ablation of the pituitary at age 60 days results in cessation of the growth of type 1 muscle fibers, and a reduction in the size of type 2 muscle fibers at 120 days of age, 60 days after hypophysectomy. The effects of food restriction, which are known to reduce pituitary hormone secretion, are not as great as hypophysectomy in inhibiting muscle fiber growth. Food restriction slowed the growth of type 1 muscle fibers (hypophysectomy abolished growth) and caused cessation of growth of type 2 muscle fibers (hypophysectomy caused atrophy).

Aging↗

Failure of hypophysectomy to correct pituitary-dependent Cushing's disease in two patients.

One woman (patient 1), aged 27 years, and one man (patient 2), aged 26 years, had pituitary surgery for pituitary-dependent Cushing's syndrome. An adenoma was identified and removed in both patients. Persistence of hypercortisolism characterized the response of patient 2 to surgery; transient hypoadrenalism, the response of patient 1. Patient 1 subsequently underwent a relapse. At the second surgery (total hypophysectomy for both patients), hyperplasia was demonstrated in patient 1, and scattered nests of adrenocorticotropic hormone (ACTH)-secreting cells were demonstrated in patient 2. Postoperatively, Cushing's syndrome persisted in both patients. Inferior petrosal sampling for ACTH during corticotropin releasing hormone stimulation verified a pituitary source of ACTH in patient 1. A decrease in cortisol secretion following hypophysectomy and subsequent cure by pituitary irradiation constitutes the evidence for pituitary origin in patient 2. Dexamethasone suppression and corticotropin releasing hormone-stimulation tests consistently suggested a pituitary cause throughout the clinical course of both patients. Computed tomographic scans after hypophysectomy revealed postoperative changes only. In both patients, panhypopituitarism, except for cortisol and ACTH, followed hypophysectomy. It may be concluded that patients with diffuse pituitary ACTH hyperplasia cannot, at present, be identified preoperatively by conventional clinical testing. Surgery for such patients may not be the therapy of choice.

Adenoma↗