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At least 19 recordsLinked to original sources

Selective fetal hypophysectomy in utero: microsurgical technique and comparisons with hypophysectomy by decapitation.

A detailed description is given of a surgical technique for selectively removing the pituitary anlage from the intrauterine fetal rat as an alternative to the more generally applied fetal hypophysectomy by decapitation. Fetuses on the 17th day of gestation were approached through a narrow opening in the uterine wall and fetal membranes. The pituitary gland was sucked out with a fine glass tube introduced from the side of the head into the space between the pons and the ventral hypothalamus, where the gland is situated. The female rat was sacrificed on the 22nd day of gestation (the day before delivery) and the surviving fetuses were preserved. On average, 20% of the operated fetuses survived until that day, 20% of which were completely hypophysectomized (microscopical examination). Operated fetuses with intact pituitaries served as surgical controls for the evaluation of selected effects of the total hypophysectomy. Initial comparisons were made with published results based on hypophysectomy by decapitation, evaluated without access to surgical controls. The two methods of fetal pituitary removal provide consistent results as regards the weight increase of adrenal and thyroid glands (retardation), thymus gland (stimulation) and testicles (no effect). On the other hand, body weight increase was not affected by selective hypophysectomy but instead slowed down after decapitation, whereas the growth in length of the humerus bone was stimulated and retarded, respectively.

Animals↗

Assessment of pituitary function after transsphenoidal hypophysectomy in beagle dogs.

Pituitary function was assessed in healthy adult beagle dogs before and after hypophysectomy. Anterior pituitary function was tested by use of the combined anterior pituitary (CAP) function test, which consisted of sequential 30-sec intravenous injections of four hypothalamic releasing hormones, in the following order and doses: 1 microgram of corticotropin-releasing hormone (CRH)/kg, 1 microgram of growth hormone-releasing hormone (GHRH)/kg, 10 micrograms of gonadotropin-releasing hormone (GnRH)/kg, and 10 micrograms of thyrotropin-releasing hormone (TRH)/kg. Plasma samples were assayed for adrenocorticotropin (ACTH), cortisol, GH, luteinizing hormone (LH), and prolactin (PRL) at multiple times for 120 min after injection. Pars intermedia function was assessed by the alpha-melanotropin (alpha-MSH) response to the intravenous injection of the dopamine antagonist haloperidol in a dosage of 0.2 mg/kg. Posterior pituitary function was assessed by the plasma vasopressin (AVP) response to the intravenous infusion of 20% saline. Basal plasma ACTH, cortisol, thyroxine, LH. PRL, and AVP concentrations were significantly lower at 10 wk after hypophysectomy than before hypophysectomy. In the CAP test and the haloperidol test, the peaks for the plasma concentrations of ACTH, cortisol, GH, LH, PRL, and alpha-MSH occurred within 45 min after injection. At 2 and 10 wk after hypophysectomy, there were no responses of plasma GH, LH, PRL, and alpha-MSH to stimulation. In four of eight hypophysectomized dogs, there were also no plasma ACTH and cortisol responses, whereas in the other four dogs, plasma ACTH and cortisol responses were significantly attenuated. The basal plasma ACTH and cortisol concentrations were significantly lower in the corticotropic nonresponders than in the responders. Plasma AVP responses were completely abolished by hypophysectomy, although water intake by the dogs was normal. Histopathological examinations at 10 wk after hypophysectomy revealed that adrenocortical atrophy was much more pronounced in the corticotropic nonresponders than in the responders. No residual pituitary tissue was found along the ventral hypothalamic diencephalon. However, in all hypophysectomized dogs that were investigated, islets of pituitary cells were found embedded in fibrous tissue in the sella turcica. A significant positive correlation was found between the number of ACTH-immunopositive cells and the ACTH increment in the CAP test at 10 wk after hypophysectomy. It is concluded that 1) stimulation of the anterior pituitary with multiple hypophysiotropic hormones, stimulation of the pars intermedia with a dopamine antagonist, and stimulation of the neurohypophysis with hypertonic saline do not cause side effects that would prohibit routine use, 2) in the routine stimulation of the anterior pituitary and the pars intermedia, blood sampling can be confined to the first 45 min, 3) the ACTH and cortisol responses to hypophysiotropic stimulation are the most sensitive indicators for residual pituitary function after hypophysectomy, 4) small islets of pituitary cells in the sella turcica, containing corticotropic cells, are the most likely source of the attenuated corticotropic response that may occur after hypophysectomy, and 5) residual AVP release from the hypothalamus after hypophysectomy is sufficient to prevent diabetes insipidus, despite the fact that the AVP response to hypertonic saline infusion is completely abolished.

Adrenocorticotropic Hormone↗

Effects of hypophysectomy on galaninergic neurons in the rat hypothalamus.

To understand better the relationship between hypothalamic galaninergic neurons and the pituitary gland, we studied the effects of hypophysectomy on hypothalamic galanin (GAL) content and distribution by radioimmunoassay and immunohistochemistry, and on GAL mRNA by Northern blot analysis. Three weeks after hypophysectomy, performed at 5 or 8 weeks of age, the hypothalamic concentrations of GAL and GAL mRNA were reduced by 30-50% in both male and female rats, compared to age- and sex-matched controls. Similar reverse-phase HPLC retention times of hypothalamic GAL were observed in intact and hypophysectomized rats. The reduction of hypothalamic GAL concentration following hypophysectomy was time-dependent, as peptide levels were unaffected one week after surgery. Immunohistochemistry showed regional differences in the effect of hypophysectomy on galaninergic neurons. In the hypophysiotropic hypothalamus, the scarce GAL immunoreactivity normally observed in the arcuate nuclei was no longer detectable in hypophysectomized rats, and the intense GAL immunoreactivity of the external zone of the median eminence progressively decreased and completely disappeared 3 and 6 weeks after hypophysectomy. In contrast, in the neurohypophyseal system, there was an increase of GAL labelling of the perikarya and emerging axons in the supraoptic and lateral-paraventricular nuclei, 1 and 3 weeks after hypophysectomy, that disappeared 6 weeks after hypophysectomy. An increase of GAL immunoreactivity was also observed in the internal zone of the median eminence 1 week but not 3 weeks after hypophysectomy. We conclude that hypophysectomy reduces the content of GAL and GAL mRNA in the rat hypothalamus. These changes are time-dependent and clearly detected after 3 weeks. The neurohypophyseal and hypophysiotropic galaninergic systems respond differently to hypophysectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Role of endocrine function tests in the evaluation of transsphenoidal hypophysectomy for advanced breast cancer.

Forty-three women underwent transsphenoidal hypophysectomy for metastatic breast cancer. Endocrine tests (luteinizing hormone, follicle-stimulating hormone, thyrotropin, prolactin and growth hormone) were done in 28 patients to evaluate the completeness of the procedure. Response of the metastatic breast cancer and duration of survival after hypophysectomy were determined and statistically compared with the posthypophysectomy hormone levels. Only one patient had an endocrinologically complete hypophysectomy, but the objective remission rate (32 percent) is comparable to the 30 to 40 percent objective remission rate reported in other studies that claim to have achieved complete hypophysectomy. No statistically significant associations were found between the levels of the hormones measured and the type of response (objective, subjective or none) to hypophysectomy. However, objective responders survived longer than nonresponders (p = 0.01). When analyzing the associations of the various hormone levels with the duration of survival after hypophysectomy, a positive correlation (p less than 0.05) of peak thyrotropin levels with duration of survival was found. Our data indicate that the clinical benefit advanced breast cancer patients received from an endocrinologically incomplete hypophysectomy is probably as great as that received from an endocrinologically complete hypophysectomy. It appears that a nonspecific disturbance of the hormonal milieu may adversely affect the growth of breast cancer. More studies are needed to elucidate the nature of the endocrine disturbance produced by hypophysectomy and its effects on hormone-sensitive tumors.

Adult↗