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Changes in serous and encephalic serotonin in hypophysectomized or adrenalectomized rats have been observed. Adrenalectomy produces a decrease of serous serotonin and an increase of the serotonin of hemispheres, base, and medulla oblongata; with hypophysectomy, serotonin is also reduced in serum and increased only in the base and medulla oblongata.
Cells from the adrenals of hypophysectomized rats (up to 28 days after operation) require less adrenocorticotropic hormone to induce one-half maximal rate of production of 3',5'-adenosine monophosphate than do cells from the adrenals of intact rats. A corresponding increase in sensitivity is reflected in the steroidogenic response to adrenocorticotropic hormone up to 2 days after hypophysectomy.
The influence of anterior pituitary hormones on the gastrointestinal tract of humans and animals has been reported. Hypophysectomy (HYPOX) in the rat causes atrophy of the intestinal mucosa, reduction of gastric secretion and intestinal absorption, and increased susceptibility to infections. To our knowledge, there are no studies on the humoral immune response of the gut-associated lymphoid tissue after HYPOX. We have reported that decreased secretion of vasopressin and oxytocin due to neurointermediate pituitary lobectomy (NIL) diminishes humoral and cell-mediated immune responses. However, no data have been published on whether NIL can affect intestinal immune responses. We analyzed the effects of HYPOX and NIL on bacterial colonization of the intestinal lumen, Peyer's patches, and spleen as well as the serum immunoglobulin G (IgG) and IgM and specific intestinal IgA levels in response to Salmonella enterica serovar Typhimurium oral infection. Results showed the following: (i) Salmonella serovar Typhimurium was eliminated from the intestinal lumen at the same rate in rats that underwent a sham operation, HYPOX, and NIL; (ii) Salmonella serovar Typhimurium colonization of Peyer's patches and spleen was significantly higher in both HYPOX and NIL rats than in sham-operated rats; (iii) serum IgG and IgM and intestinal IgA against surface proteins of Salmonella serovar Typhimurium were significantly lower in HYPOX and NIL rats than in sham-operated rats; and (iv) compared to NIL rats, higher Peyer's patch and spleen bacterial colonization and decreased IgG, IgM, and IgA production were observed in HYPOX rats. We conclude that hormones from each pituitary lobe affect the systemic and gastrointestinal humoral immune responses through different mechanisms.
Mendenhall's syndrome comprises insulin-resistant diabetes, pineal hyperplasia, and various somatic anomalies. A boy with this condition now aged 12 years is reported; a similarly affected sibling died aged 7.8 years. Hypophysectomy has been of short-term benefit, but the problems of insulin resistance persist. On the basis of monocyte-binding studies it seems likely that in this condition there is an inherited deficiency of insulin receptors.
Results are reported in 35 patients with prolactinomas who underwent pituitary surgery within the past five years. After surgery prolactin concentrations became normal in 26 patients and symptoms were alleviated, and nine normal pregnancies were achieved in seven women, including all those who had complained of infertility. Normal prolactin concentrations were restored in 16 of 17 patients with tumours 5-19 mm in diameter but in only six of 11 with tumours less than or equal to 4 mm and four of seven with tumours greater than or equal to 20 mm. Normal prolactin concentrations were restored in all those with preoperative concentrations below 1000 mU/l but in none of those with concentrations above 10 000 mU/l. Although not all of the patients were followed up for five years, hyperprolactinaemia did not recur in any patient whose prolactin concentration had returned to normal six weeks after surgery. This included 16 patients with macroprolactinomas (greater than 10 mm in diameter), who were followed up for from two to five years. These data contrast strikingly with those reported by others at similar stages of follow up and show clearly that partial hypophysectomy offers an acceptable alternative treatment for selected patients with prolactinomas.
Hypophysectomy (HYPX) in genetically obese (fa/fa) Zucker rats significantly reduced body weight and energy gains and stimulated energy expenditure (by 34%), the thermic response to food (by 144%), and brown adipose tissue (BAT) mitochondrial GDP-binding capacity (by 190%) compared with pair-fed, sham-operated obese rats. These changes in energy balance in obese HYPX rats were reversed by corticosterone replacement (1 mg/day), but the increased BAT activity was only partly restored to normal. HYPX had only small effects on energy balance in lean Zucker rats compared with pair-fed, sham-operated lean controls but increased the acute thermic response to food and BAT mitochondrial GDP-binding capacity; these effects were inhibited by replacement of HYPX rats with corticosterone. The results suggest that alterations in the hypothalamic-pituitary-adrenal axis play a fundamental role in the development and maintenance of genetic obesity.
To investigate whether growth hormone (GH) and 17beta-estradiol (E2) replacement can prevent osteopenia induced by pituitary and ovarian hormone deficiency [by hypophysectomy and ovariectomy (HX+OV)], we administered relatively low doses of GH (2.3 IU x kg(-1) x day(-1)) and E2 (100 microg x kg(-1) x wk(-1)) in experiment 1 and relatively high doses of GH (13.5 IU x kg(-1) x day(-1)) and E2 (3,500 microg x kg(-1) x wk(-1)) in experiment 2 to 2-mo-old HX+OV Sprague-Dawley rats for 6 wk. Our data show that the HX+OV of rats results in diminished periosteal bone formation, longitudinal bone growth, and decreased cancellous bone volume. Administration of either the low or high dose of GH to these rats increased their systemic growth, serum levels of osteocalcin, and cortical bone formation. Either low or high doses of GH or E2 alone only partially prevent cancellous bone loss. However, the combined treatment of GH plus E2 resulted in an additive increase in the cancellous bone mass. We conclude that the additive effect of GH plus E2 on cancellous bone is attributed to the suppressive effect of E2 on bone resorption and the anabolic effect of GH on bone formation.
The effects of long-term hypophysectomy on renin secretion and the renin and drinking responses to isoproterenol were investigated in male rats. Drinking responses to angiotensin II, hypertonic saline, and water deprivation for 24 h were also measured. Plasma renin activity and plasma angiotensin II were variably lower in rats that had been hypophysectomized for 21 days than in intact controls. Angiotensinogen was also reduced, but plasma renin concentration was not. Isoproterenol produced a smaller increase in plasma renin activity in hypophysectomized rats than it did in controls, but with the one dose of isoproterenol that was tested, the increase in plasma renin concentration was comparable in the two groups. However, the drinking responses to isoproterenol were greater in the hypophysectomized rats. The drinking responses produced by infusion of angiotensin II were also greater, but the responses to infusion of hypertonic saline and to 24 h of water deprivation were not. The data suggest that in rats hypophysectomized for 21 days the circumventricular organs that mediate thirst are hyperresponsive to circulating angiotensin II, possibly because the relatively low circulating angiotensin II levels permit the upregulation of angiotensin II receptors in these structures.
Potassium depletion is involved in the pathophysiology of metabolic alkalosis. In the present study, the expression of renal acid-base transporters that are involved in HCO3- reabsorption was studied in potassium depletion. Rats fed potassium-deficient (KD) diet developed significant hypokalemia at 14 days (serum K+ 1.9 +/- 0.2 in KD vs. 4.2 +/- 0.2 meq/l in control, P < 0.01) but not at 6 days (3.8 +/- 0.3 in KD vs. 4.1 +/- 0.3 meq/l in control, P > 0.05). Kidney mRNA for colonic H(+)-K(+)-adenosinetriphosphatase (H(+)-K(+)-ATPase, cHKA) increased by approximately 3- and 11-fold at 6 and 14 days of KD diet, respectively, indicating that increased expression preceded the onset of hypokalemia. The expression of Na+/H+ exchanger 3 (NHE-3) mRNA and its cognate protein remained unchanged at 6 and 14 days of KD diet. The mRNA levels for NHE-1, NHE-2, and NHE-4 also remained unchanged at 6 and 14 days of KD diet. Hypophysectomized (HPX) rats fed KD diet for 14 days developed similar hypokalemia. However, the expression of cHKA mRNA in the kidney was decreased by approximately 80% in potassium-depleted (HPX+KD) rats (P < 0.01 vs. KD only). Hypophysectomy did not affect the mRNA levels for either gastric H(+)-K(+)-ATPase (gHKA) or NHE isoforms in KD animals. Thus potassium depletion increases expression of cHKA in the kidney but not that of gHKA or NHE isoforms. The signal for this increase appears to precede hypokalemia. Furthermore, the data suggest that pituitary hormone(s) plays an important and novel role in the regulation of cHKA.
Stereotactic radiofrequency transfrontal hypophysectomy was carried out in 7 patients with osseous metastasis from prostatic carcinoma resulting in intractable pain. 86% experienced significant pain relief with 5 of 7 demonstrating marked decrease in medication requirement and improved level of function. The procedure was done under local anesthesia only with no mortality and minimal morbidity. Total destruction of the pituitary gland and the development of diabetes insipidus were shown not to be necessary conditions for pain relief.
Clinical indications and technical details of RF hypophysectomy were reviewed. Evaluation of serveral hundred procedures toward pathologic and symptomatic amelioration ofmetastatic breast cancer and diabetic retinopathy, and also a few cases of intrasellar tumor, indicated sufficient benefit for endorsement in selected patients.
Immunoreactive thyroid-stimulating hormone (IR-TSH) has been detected in the hypothalamus and is released in vitro by a calcium-dependent mechanism when the tissue is depolarized. Recently, immunocytochemical studies have revealed that IR-TSH is present in thyrotropes in the pars tuberalis. Therefore, because these thyrotropes are associated with the median eminence, the area with the highest concentration of IR-TSH, it is of interest to determine if 'hypothalamic' IR-TSH is from neural or pituitary cells. We addressed this issue by studying the effects of hypophysectomy, thyroidectomy, or chronic administration of triiodothyronine (T3) or thyroxine (T4) on the distribution and in vitro release of IR-TSH in the hypothalamus. We reasoned that, if hypothalamic IR-TSH is dependent on the thyrotropes of the pars tuberalis, then changes in hypothalamic IR-TSH concentration and release should be parallel to those measured in pituitary extracts. IR-TSH was measured in tissue extracted in ice-cold 2% NaCl, with a final pH of 4.5. For the in vitro studies, tissues were incubated for 20-min periods in Krebs-Ringer bicarbonate buffer at 37 degrees C. In untreated rats, the concentration of IR-TSH is greater in the ventral than the dorsal portion of the hypothalamus (39.3 +/- 8.2 vs. 4.0 +/- 1.5 ng/mg wet wt.). Upon finer dissection of the hypothalamus into median eminence and anterior, middle, and posterior portions of the remainder, IR-TSH was only detectable in the middle hypothalamus (5.3 +/- 1.5 ng/mg), and the median eminence (149 +/- 41 ng/mg).(ABSTRACT TRUNCATED AT 250 WORDS)
Prompted by immunohistochemical reports of prolactin-like immunoreactivity in cell bodies within the rat hypothalamus, a study was undertaken to quantitate the immunologic and biologic activity of this material. Hypothalamic concentrations of prolactin-like immunoreactivity averaged 402 +/- 23 pg/mg of protein (n = 30). 97% recovery of rat prolactin standards added to homogenates of hypothalamus insured that neuronal tissue, as prepared for these studies, did not interfere with the radioimmunoassay of rat prolactin. Examination of the elution profile from Sephadex G-75 columns of the prolactin-like immunoreactivity in hypothalamic extracts showed that the majority of hypothalamic prolactin-like substance was of a larger molecular size than pituitary prolactin. While increasing amounts of brain extract progressively displaced more I125 prolactin from antibody-binding sites, the displacement curve produced by adding hypothalamic extract was not parallel to that produced by the addition of increasing amounts of anterior pituitary prolactin standards of rat origin. Hypothalamic extracts from hypophysectomized animals, analyzed for biologic activity in the Nb2 lymphoma cell assay, revealed prolactin-like bioactivity, but the bioactivity/immunoactivity (B/I) ratios for hypothalamic extracts were significantly lower than the B/I ratios for pituitary prolactin (0.71 +/- 0.04 for pituitary, vs. 0.19 +/- 0.06 in the hypothalamus; p less than 0.001). Hypophysectomy, which led to the expected fall in serum prolactin to undetectable levels, and restraint stress, which resulted in a statistically significant 4-fold rise in serum prolactin, caused no change in prolactin concentrations in the hypothalamus, indicating that brain prolactin-like substance is regulated independently of pituitary prolactin and circulating serum prolactin levels.
Complex interactions of the pituitary, hypothalamus, and pineal involving MIF-1 (Pro-Leu-Gly-NH2) were shown many years ago. One of the largest changes consisted of increased amounts of an MIF-1-like material in the plasma of hypophysectomized rats as measured by the skin lightening of darkened frogs. The present study used radioimmunoassay to measure immunoreactive Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) in intact, hypophysectomized, pinealectomized, and superior cervical ganglionectomized (SCG) rats. Samples were collected every 4 h for 24 h. Plasma concentrations of Tyr-MIF-1-like immunoreactivity were higher in hypophysectomized rats and lower in pinealectomized rats than in the intact or SCG groups, which were not reliably different from each other. In most groups, the highest plasma concentrations appeared to occur about 04.00 h, a time at which brain concentrations of Tyr-MIF-1-like immunoreactivity were low. However, no diurnal rhythm in plasma was seen in the pinealectomized rats. At none of the times did brain concentrations of immunoreactive peptide differ among the four groups. By high-performance liquid chromatography of plasma, the main peak of immunoreactivity was found to elute at the same position as Tyr-MIF-1, supporting the natural occurrence of this tetrapeptide. Thus, this study demonstrates that the concentration of immunoreactive Tyr-MIF-1 in plasma is increased by hypophysectomy.
The binding of 125I-labeled rat prolactin (125I-rat PRL) to membranes from different regions of the rat brain was studied. Among these regions the hypothalamus showed the highest specific binding. Clearly detectable specific binding was also observed in substantia nigra, whereas it was very scanty in other brain regions. No significant sex differences in PRL binding to various brain regions were observed, except for hypothalamus where a higher binding was observed in female rats. The binding of 125I-rat PRL to hypothalamus from female rats was inhibited in a dose-dependent manner by both unlabeled rat and ovine PRL but not by several other polypeptide hormones. Scatchard analysis of the binding revealed the presence of the binding sites with low capacity and high affinity for rat ligand. Ovariectomy markedly decreased PRL binding in the hypothalamus; an even more pronounced decrease was found after hypophysectomy of female animals. A treatment with estradiol restored the PRL binding in the ovariectomized rats to above normal levels. These results of in vitro biochemical analysis together with the experimental modulation of hormonal status provide strong preliminary evidence for the presence of PRL binding sites in rat brain.
Rat fetuses were subjected to selective hypophysectomy in utero on day 16, 17 or 18 of gestation and inspected on day 22 (the day before birth). The survival rate of fetuses operated on day 17 and 18 was about 20 and 50%, respectively. Losses were mostly caused by the surgery preceding the removal of the pituitary, and no significant survival-promoting activity of the gland could be demonstrated. The surgical injuries, as such, also reduced the weight increase substantially. Still, the loss of the pituitary was followed by a further reduction in weight gain, which on day 22 was about 10% lower than that of the sham-operated fetuses.
Hypophysectomy performed in 25- to 26-day-old Wistar rats leads within 1 years to the formation of ovarian testis-like tubes and epithelial cellular cords which are typical structures in the senile ovaries of normal 24-month-old rats. Testis-like tubes represent an unusual late stage of follicular degeneration; the origin of the cords is more complex; the revival of cell differentiation from stroma and/or rete ovarii in the absence of the pituitary is hypothesized. At 16 months of age, cords proliferate and are responsible for ovarian weight increase to almost twice the minimal weight seen 4 months after the operation. Variability in cord proliferation is considerable from one rat to another, but also between the two ovaries of the same animal. Thus, an intrinsic age-related ovarian factor is implicated in cord proliferation. From this study, it is inferred that during intact rat senescence, intrinsic ovarian aging is responsible for the proliferation of cords, whereas their induction depends on a hypothalamic-hypophyseal imbalance occurring at about 1 year of age.
Morphometrical analyses were carried out on muscle fibres from cross-sectional areas of the medial head of gastrocnemius muscles from 5 groups each of 4 male Wistar rats representing young (aged approximately 100 days), medium-aged (400 days), old (1,000 days), old hypophysectomized (1,000 days) and old food-restricted (1,000 days) rats. Approximately 18,000 muscle fibres were measured in each group. Rats were hypophysectomized when young at 60-70 days and food restriction began at the same age. The results show that there is a reduction in type 2 fibre size (measured as the mean equivalent circle diameter) from 59.7 micron in medium-aged controls to 50.3 micron in old controls, but there is no significant difference between the sizes of type 2 fibres in controls, hypophysectomized or food-restricted rats in old age. Analysis of type 1 fibres demonstrated no differences between young, medium-aged and old controls and the old food-restricted group, but type 1 fibres in the old hypophysectomized group (45.5 micron) were significantly smaller than in the old controls (54.6 micron) and old food-restricted rats (58.5 micron). In old controls there is a 4-fold increase in the range of fibre sizes (coefficient of variation) for type 1 fibres and a 2-fold increase for type 2 fibres, indicating fibre atrophy and hypertrophy. Long-term hypophysectomy is more effective than food restriction in preserving the smaller range of the coefficient of variation of fibre size seen in young controls.