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PubMed1979

The effect of hypophysectomy on rat chorionic somatomammotropin as measured by prolactin and growth hormone radioreceptor assays: possible significance in maintenance of somatomedin generation.

We have previously reported that serum somatomedin concentrations are maintained in pregnant rats after hypophysectomy. Because rat chorionic somatomammotropin (rCS) might replace pituitary GH during pregnancy, the concentration of rCS was measured at intervals after hypophysectomy on day of pregnancy. By day 16 of pregnancy, the serum rCS of hypophysectomized (hypox) rats was actually higher than that of normal pregnant rats when measured by a lactogenic radioreceptor assay. Increased levels of lactogenic radioreceptor activity (L-RRA) were maintained in the serum of hypox rats throughout the remainder of pregnancy. The GH radioreceptor activity (GH-RRA) of serum of hypox pregnant rats was also greater than that of normal rats during the last days of pregnancy, but the activity was only about 1/20th that of the L-RRA with the assays employed. There was no significant difference between placental L-RRA and GH-RRA of normal and hypox pregnant rats. The difference in concentration could not be attributed to differences in the number of fetuses. We conclude that the high levels of rCS were sufficient to maintain serum somatomedin concentration in hypox pregnant rats. This effect of rCS could have been due to binding by GH or PRL receptors of the maternal liver.

Animals↗
PubMed1989

Prolactin maintains relaxin and progesterone secretion by aging corpora lutea after hypophysial stalk transection or hypophysectomy in the pig.

Porcine corpora lutea persist beyond 150 days in hysterectomized animals compared with about 114 days during normal pregnancy. To explore the mechanism(s) regulating the peak release of relaxin and secretion of progesterone by aging corpora lutea and to examine the direct effect of purified porcine (p) PRL on such corpora lutea, hypophysial stalk transection (HST), hypophysectomy (HYPOX) with or without PRL replacement, and sham operation control (SOC) were conducted on day 110 (estrus = day 0) on purebred Yorkshire gilts that were hysterectomized on days 6-8. The pPRL (0.5 mg every 6 h daily) or PBS (0.5 ml every 6 h daily) was given iv from days 110-120. HYPOX + pPRL, HYPOX + PBS, HST + PBS, and SOC + PBS formed four experimental groups. Peak relaxin concentrations in peripheral plasma (mean values ranged from 22-24 ng/ml) occurred on about day 113 for all groups [113.4 +/- 0.3 days (+/- SE)] regardless of the different surgical interventions. After peak release, relaxin decreased steadily in the HYPOX + PBS group, falling to less than 1.0 ng/ml by 6 days later, whereas relaxin in other groups remained elevated (approximately 7 ng/ml). In the HYPOX plus PBS group, progesterone decreased abruptly, remaining below 1 ng/ml from 1 week onward, lower (P less than 0.01) than that in controls (approximately 19 ng/ml); in the HYPOX + pPRL group, progesterone levels (approximately 17 ng/ml) remained similar (P greater than 0.05) to those in controls (approximately 19 ng/ml) and the HST + PBS group (approximately 15 ng/ml). These results clearly reveal that the pituitary gland plays no direct role in regulating the timed peak release of relaxin from aging corpora lutea in hysterectomized gilts and that the peak release of relaxin on about day 113 is preprogrammed and inherent within such aging luteal cells. This study provides strong evidence that purified pPRL maintains both relaxin and progesterone secretion as well as the morphology of aging corpora lutea for at least 10 days after hypophysectomy in hysterectomized gilts.

Animals↗
PubMed1989

Alterations in adipogenic and mitogenic activity of porcine serum in response to hypophysectomy.

The importance of the pituitary in postnatal regulation of peripheral preadipocyte proliferation and differentiation was examined by hormone supplementation of hypophysectomized pig serum in primary cultures of preadipocyte and stromal-vascular cells derived from rat inguinal adipose tissue. Hypophysectomized pig serum promoted at least 25% less preadipocyte proliferation, less differentiation of sn-glycerol-3-phosphate dehydrogenase activity, and less histochemical differentiation than serum from intact pigs. Porcine GH supplementation of hypophysectomized serum-stimulated [3H]thymidine incorporation by preadipocytes and stromal cells and also histochemical differentiation of preadipocytes, but not enzymatic differentiation. Insulin-like growth factor I (IGF-I) stimulated [3H]thymidine incorporation by preadipocytes and stromal cells. Enzyme differentiation by developing cells was stimulated by IGF-I. Hydrocortisone supplementation of hypophysectomized serum inhibited [3H]thymidine incorporation and stimulated enzymatic differentiation. Thyroid hormones (T3 and T4) stimulated [3H]thymidine incorporation by preadipocytes in a dose-responsive manner when supplemented to hypophysectomized serum. Thyroid hormones stimulated differentiation of enzyme activity at the lowest concentrations examined. The mitogenic effects of GH, IGF-I, and T4 were not specific to the preadipocyte population, since the stromal-vascular cells responded in a similar manner. However, hypophysectomy resulted in a specific reduction in preadipocyte proliferation while stimulating multiplication of stromal-vascular cells. These results suggest that these hormones are nonspecific mitogens in adipose tissue, while unidentified factors of pituitary origin may be important for the specific regulation of proliferation of preadipocytes. Additionally, hypophysectomy appears to remove mitogenic inhibitors that are specific for the stromal-vascular cells.

Adipose Tissue↗
PubMed1990

Effect of hypophysectomy on growth hormone receptor gene expression in rat tissues.

Two cDNA probes derived from the nucleic acid sequence for the rabbit GH receptor were used to study RNA samples from normal and hypophysectomized (hypox) rat tissues by Northern analysis. Results obtained with a probe that contained a nucleotide sequence corresponding to part of the extracellular domain of the GH receptor indicated that rat liver, gastrocnemius muscle, and epididymal fat each contain a 4.4-kilobase (kb) message and one or more shorter messages that appear to be homologous to the rabbit GH receptor message. The other probe, which contained a nucleotide sequence that corresponds to the intracellular domain of the GH receptor, detected only one 4.4-kb message in these rat tissues. These results suggest that rat tissues may synthesize several forms of the GH receptor, but only one form that contains a region homologous to the intracellular domain of the rabbit liver GH receptor. Hypophysectomy increased the abundance of the 4.4-kb message 5-fold in muscle and reduced it by a factor of 2 in adipose tissue. No significant difference was seen between GH receptor message levels of normal and hypox rat liver when the results were expressed as a fraction of the total RNA. The level of the beta-actin message was also measured in liver, muscle, and fat from normal and hypox rats. No significant differences were found when the message levels in normal rats were compared to those for the corresponding tissue in hypox rats. When normalized to the beta-actin message levels, a significant increase was seen in the relative amount of the GH receptor mRNA in muscle and liver of hypox rats. The increased levels of the GH receptor message in muscle and liver and the simultaneous decreased level in fat suggest that GH receptor synthesis may be regulated selectively in these tissues by hormonal factors that are altered by hypophysectomy.

Adipose Tissue↗
PubMed1976

Effect of hypophysectomy on immunocytochemically demonstrated gonadotropin-releasing hormone in the rat brain.

The objective was to determine the effect of hypophysectomy on the store of gonadotropin-releasing hormone (GnRH) in certain parts of the brain as revealed by immunocytochemistry. The antiserum used was prepared against synthetic GnRH conjugated with limpet hemocyanin. No change was observed in the store of GnRH in the organum vasculosum of the lamina terminalis or in the cephalic segment of the median eminence GnRH was depleted severely from the central and caudal (junction with the infundibular stem) segments of the median eminence. GnRH was not found in the axons of magnocellular neurons that regenerate during repair of the median eminence-pituitary stalk after hypophysectomy.

Animals↗
PubMed1994

Influence of hypophysectomy on renal proteoglycans and their modulation by insulin-like growth factor-I and its receptor.

Hypophysectomy leads to growth retardation of the animals, which is believed to be related to the deficiency of certain growth factors influencing the metabolism and synthesis of glycoproteins. Conceivably, the extracellular matrix proteins (ECM) are also affected, in particular the sulfated proteoglycans (PGs). In this study, we investigated the status of the ECM proteins and sulfated PGs, and the expression and de novo synthesis of insulin-like growth factor-I (IGF-I) receptor (IGF-IR) in hypophysectomized (Hx) rats. The studies were extended to ascertain the effect of IGF-I on the de novo synthesis of glomerular ECM glycoproteins in Hx rats. An organ perfusion system was used in which isolated rat kidneys were radiolabeled with either [35S]sulfate or [35S]methionine, after which IGF-IR and ECM macromolecules were isolated and characterized by biochemical and tissue autoradiographic procedures. Hypophysectomy resulted in a fall in IGF-I levels in serum and isolated renal glomeruli. Reduced synthesis of ECM proteins, i.e. type IV collagen, laminin, and sulfated PGs, and reduced synthesis and mRNA expression of IGF-IR were observed in the glomeruli of the Hx rats. Tissue autoradiographic studies revealed a reduced grain density (concentration of radiation) over various cell types of the glomerulus. After inclusion of IGF-I in the perfusion medium not only was synthesis restored to normal in Hx rats, but it far exceeded the control basal values in the intact animals. Under the influence of IGF-I, the magnitude of increased synthesis of the ECM proteins, in particular the sulfated PGs, was highly accentuated in the kidneys of the Hx group compared to the controls. Also, a remarkably increased [35S]sulfate incorporation was observed in the glomerular mesangial cells. The analysis of IGF-IR by specific binding studies revealed a decreased concentration of the receptors, but an increased IGF-I-binding affinity, the latter of which probably contributed to the IGF-I-induced accentuated synthesis of renal glomerular PGs in the Hx group.

Animals↗
PubMed1999

Long-term growth after hypophyseal stalk transection and hypophysectomy of beef calves.

Hypothalamic hormones regulate episodic and basal secretion of hormones from the anterior pituitary gland that affect metabolism and growth in cattle. This study focused on long-term growth in young calves subjected to hypophysectomy (HYPOX), hypophyseal stalk transection (HST), and sham operation control (SOC). Cross-bred (Hereford x Aberdeen Angus) and Hereford, and Aberdeen Angus calves were HYPOX (n = 5), HST (n = 5), or SOC (n = 8) at 146 +/- 2 days of age, whereas another group was HST (n = 5) or SOC (n = 7) at 273 +/- 5 days of age. Body weight was determined every 21 days from birth to 1008 days of age. Anterior vena cava blood was withdrawn at 4-day intervals from day 64-360 for RIA of GH, TSH, T4, T3, and LH, and at 20-min intervals for 480 min to determine episodic hormone secretion. Daily feed intake was determined in HST and SOC calves during an 80-day period. Birth weight averaged 35 +/- 1 kg (+/- SE) and was 142 +/- 4 kg at 126 days and 208 +/- 8 kg at 252 days before surgery. From day 146-1008, growth was arrested (P < 0.001) in HYPOX (0.06 +/- 0.01 kg/day) compared with SOC (0.50 +/- 0.04 kg/day) calves. Growth continued but at a significantly lower rate (P < 0.05) in calves HST at 146 days (0.32 +/- 0.07 kg/day) and 273 days (0.32 +/- 0.06 kg/day) compared with SOC (0.50 +/- 0.09 kg/day). Growth continued to be impaired to 1008 days, but more so in those HST at 146 days (432 +/- 43 kg BW) than 273 days (472 +/- 5 kg BW) and less (P < 0.05) than SOC (586 +/- 37 kg BW). Daily feed intake was consistently less (P < 0.05) in HST compared with SOC calves. Although episodic GH secretion was abolished and peripheral serum GH concentration remained consistently lower in HST (2.4 ng/ml) than SOC (5.5 ng/ml; P < 0.01), the calves continued to grow throughout 1008 days. Peripheral serum TSH concentration was less (P < 0.05) HST compared with SOC calves. There was an abrupt decrease (P < 0.001) in serum T4 (4-fold) and T3 (3-fold) concentration after surgery that remained to 360 days in HST compared with SOC calves. At the time calves were killed, pituitary gland weight was markedly reduced (P < 0.001) in HST (0.18 +/- 0.01 g/100 kg BW) compared with SOC (0.54 +/- 0.03 g/100 kg BW). Histological examination of pituitary glands from HST calves indicated the persistence of secretory GH and TSH cells in the same areas of the adenohypophysis as SOC calves. Coronal sections of the gland stained with performic acid-Alcian blue-periodic acid-Schiff-orange G, revealed GH and TSH secreting cells in HST calves similar to controls. These results indicate that long-term growth continues, but at a slower rate, after hypophyseal stalk transection of immature calves in spite of complete abolition of episodic GH secretion and consistently decreased basal secretion of GH, TSH, T4, and T3 compared with sham-operated animals. Growth was abolished after hypophysectomy of immature calves in which circulating GH and TSH was undetectable.

Animals↗
PubMed1978

Changes in NSILA-S in response to somatotropin administration and hypophysectomy.

The effects on the serum levels of NSILA-S of the administration of human GH (hGH) or of hypophysectomy have been studied. hGH given im (5 mg daily for 3 days) raised the NSILA-S levels of three GH-deficient subjects into the normal range. Significant elevations of NSILA-S were also seen in three normal subjects given im GH. In the same groups of three normal and three GH-deficient subjects, 5 mg hGH administered iv induced an elevation of NSILA-S within 15-60 min. Hypophysectomy in three acromegalics and one subject with a chromophobe adenoma was followed by significant falls of serum NSILA-S. These studies provide further evidence of the dependence of NSILA-S levels on GH.

Acromegaly↗
PubMed2004

Functional hypophysectomy simply by neck-strangulation in the rat: applications for ACTH and LH assays.

The classical methods for hypophysectomy require a long training-period and at the end of each experiment, it is required to check any undue remnant of the hypophyseal tissue in the sella turcica, and there must be exclusion of such datum with the remnant from the experimental group. The present method for functional hypophysectomy by neck-strangulation in the rat is very simple to perform so that even an experimenter with little experience can become easily accustomed to the technique and obtain a number of functionally hypophysectomized preparations at any time he intends, with no need to check the remnant. The cerebral blood circulation of vertebrally dislocated rats was immediately intercepted by means of neck-strangulation and artificially respired. Fifteen minutes after intravenous injection of ACTH (0.1 - 3.2 mU/rat) or LH (312.5 - 2500 ng/rat), blood was sampled from the vena cava, and sera were examined for corticosterone or testosterone by radioimmunoassay. A linear dose-response relationship was obtained within a dose range of 0.2 - 1.6 mU/rat of ACTH and 312.5 - 1250 ng/rat of LH. In the ACTH assay, parapharyngeally hypophysectomized rats were compared. It was found that the sensitivity of functionally hypophysectomized preparations was 2.72 times higher than that of the parapharyngeally hypophysectomized rats.

Adrenocorticotropic Hormone↗
PubMed2003

Prophylactic efficacy of desmopressin acetate for diabetes insipidus after hypophysectomy in the dog.

The prophylactic efficacy of desmopressin acetate (DDAVP) on diabetes insipidus (DI) after hypophysectomy was investigated in the dog. In the control group, hypernatremia with a plasma level of 155 mEq/l or higher persisted for 12 hr from the 4th to the 16th hour after hypophysectomy, and symptoms of DI developed within five days after surgery. In the DDAVP treatment group, these changes were not observed, showing that administration of DDAVP (4 microg, installation, twice daily) effectively prevented hypernatremia that develops immediately after surgery and DI-like symptoms that persists for about one week after surgery.

Animals↗
PubMed2003

Transsphenoidal hypophysectomy for four dogs with pituitary ACTH-producing adenoma.

Four dogs diagnosed as pituitary-dependent hyperadrenocorticism were treated with transsphenoidal hypophysectomy and postoperative hormone supplementation therapy. On histological examination of the resected tissues, the tumors were ACTH-producing adenoma of the anterior lobe. Clinical signs such as alopecia and calcinosis cutis, as well as endocrinological abnormalities, were markedly alleviated after surgery. The clinical courses of these 4 dogs suggest that transsphenoidal hypophysectomy may be a useful treatment for pituitary-dependent hyperadrenocorticism.

Adenoma↗
PubMed1980

The effect of hypophysectomy and hypophysis-transplantation on the secretion of gut glucagon immunoreactivity and gut glucagon-like immunoreactivity in depancreatized dogs.

The role of hypophysis in the regulation mechanism of the secretion of gut glucagon immunoreactivity (gut GI) that was measured using C-terminal specific glucagon antiserum after pancreatectomy, and gut glucagon-like immunoreactivity (gut GLI) that was obtained by subtracting GI from total glucagon-like immunoreactivity (total GLI) which was measured using non-specific glucagon antiserum, was investigated in depancreatized dogs. Plasma glucose, gut GI and gut GLI levels were found to increase in totally depancreatized dogs. The former two showed a significant decrease after hypophysectomy, and were reversed by the hypophysis-transplantation, while gut GLI was not affected either by hypophysectomy or hypophysis-transplantation. Intramuscular injections of human growth hormone (HGH) or adrenocorticotropic hormone-Z (ACTH-Z) to depancreatized-hypophysectomized dogs had no effect on plasma glucose level or gut GI. It is concluded that hypophysis may promote the secretion of gut GI after pancreatectomy, but not of gut GLI. Gut GI seems to regulate plasma glucose level after pancreatectomy. However, the precise regulation mechanism of gut GI by the hypophysial hormone after pancreatectomy is not clarified yet.

Adrenocorticotropic Hormone↗
PubMed1976

Thyroid function in acromegaly before and after transsphenoidal hypophysectomy followed by cryoapplication.

Thyroid function was studied in acromegaly before and after transsphenoidal hypophysectomy followed by cryoapplication. The clinical material comprised 36 euthyroid, 1 hypothyroid and 3 hyperthyroid patients. In addition to the usual thyroid parameters a standard thyrotrophin-releasing hormone (TRH) stimulation test using 200 mug of synthetic TRH given iv was used. In untreated acromegaly with euthyroidism the response of serum TSH to TRH was significantly less than in normal controls, the increment being 7.1 mU/1 vs. 12.5 mU/1. In 23% of the patients the response was subnormal (less than 3.0 mU/1). The total thyroxine was significantly higher than in controls. Goitre occurred in 53% of the patients. After operation 3 patients became hypothyroid. In 30% of the patients remaining euthyroid the response to TRH was subnormal and the mean response in this group was close to the lower normal limit of 3.0 mU/1. In 7 patients who showed a subnormal response to TRH before or shortly after the operation there was a gradual increase and normalization of the response during the next few years. A subnormal, and also a low normal response to TRH before or after hypophysectomy does not necessarily indicate an increased risk for the development of hypothyroidism, and indeed the pituitary remnant seems to have a remarkable capacity for regeneration. In the hypothyroid patient there was a low normal response to TRH, the reason being unknown. In one of the hyperthyroid patients the basal TSH level was 6.5 and 8.9 mU/1 on two occasions in the thyrotoxic phase, showing a small response to TRH. The possibility that hyperthyroidism was due to increased secretion of TSH is discussed but not claimed proven. The incidence of hyperthyroidism in a large material of acromegaly from this department equals 9% which is above the prevalence of hyperthyroidism in the general population in Finland, indicating that acromegaly in one way or another seems to increase the incidence of manifest thyrotoxicosis.

Acromegaly↗
PubMed1989

Effect of hypophysectomy on the growth and development of the sheep adrenal gland: a morphometric study.

We have investigated the effect of gestational age and fetal hypophysectomy on the growth and development of the adrenal gland of the fetal sheep. The area of the fetal sheep adrenal medulla increased significantly (P less than 0.05) from 3.21 +/- 0.42 mm2 at 90-107 days to 6.09 +/- 0.26 mm2 at 120-126 days of gestation and there was a further significant increase (P less than 0.05) in the newborn period to 9.48 +/- 0.85 mm2. The adrenomedullary area of the hypophysectomised fetal sheep (7.47 +/- 1.10 mm2) was not significantly different from that of the fetal sheep at 140-146 days of gestation or from that of the newborn lamb. The ratio of the area of the adrenal occupied by the cells which contained adrenaline (adrenaline zone) to the area of the adrenal occupied by the cells which contained noradrenaline (noradrenaline zone) was unchanged between 90 days of gestation and 12 days after birth. After hypophysectomy, the ratio of the adrenaline to noradrenaline zone was not significantly different from that in the adrenal medulla of the 140-146 days fetal sheep and the 10-12 days newborn lamb.

Adrenal Cortex↗
PubMed1992

Immunoreactive ACTH in the cerebrospinal fluid of the rat: decrease after mediobasal hypothalamic lesion and hypophysectomy, increase after adrenalectomy.

The effect of various anaesthetics and of the manipulations of the hypothalamo-pituitary-adrenocortical system (hypophysectomy, adrenalectomy and lesion of the mediobasal hypothalamus) was studied on immunoreactive-ACTH levels in the plasma and in the cerebrospinal fluid in the rat. The anaesthetics used (Hypnorm, pentobarbital, urethan and Ketanest) were without effect on immunoreactive-ACTH concentration in the cerebrospinal fluid. Immunoreactive-ACTH was significantly decreased after hypophysectomy and elevated after adrenalectomy in both cerebrospinal fluid and plasma. Destruction of the mediobasal hypothalamus resulted in reduced immunoreactive-ACTH content in the cerebrospinal fluid (about 20% of control) in both experiments, whereas immunoreactive-ACTH levels in the plasma of the lesioned rats were lower only in one of the two experiments performed. These data suggest that the main source of the immunoreactive-ACTH in the cerebrospinal fluid of the rat is the hypothalamus; the contribution of the pituitary gland being less than 50% of the radioimmunoassayable ACTH.

Adrenalectomy↗
PubMed1978

Effect of fetal hypophysectomy on the initiation of parturition in the goat.

Fetal hypophysectomy performed between 97 and 130 days of gestation caused a significant (P is less than 0.005) prolongation of pregnancy in 5 goats in which every fetus was treated. Three of these goats gave birth spontaneously. Sham surgery or hypophysectomy of one fetus of twins had no effect on gestation length. Hypophysectomized kids, delivered after prolonged pregnancy, were significantly heavier than normal term kids (P is less than 0.005) and had lighter adrenals (P is less than 0.025). Measurements of maternal peripheral plasma concentrations of progesterone and total unconjugated oestrogens showed that the changes in goats carrying hypophysectomized fetuses were similar to those of normal pregnancy except that the prepartum oestrogen peak was absent, whether or not parturition occurred spontaneously.

Adrenal Glands↗
PubMed1975

Binding of human chorionic gonadotrophin by rat testis: effect of sexual maturation, cryptorchidism and hypophysectomy.

The specific binding of 125I-labelled human chorionic gonadotrophin (HCG) by rat testicular homogenate as compared with isolated Leydig cells differs with respect to total binding capacity but not to the dissociation constant (Kd) as revealed by Scatchard analysis. The maximal binding capacity for [125I]HCG of crude testicular homogenate was 95 ng/g rat testis. Hypophysectomy causes a decline in binding capacity within the first three days but on the 20th and 30th day after hypophysectomy the relative binding capacity no longer differs from that of controls. Binding capacity is enhanced in cryptorchid testes relative to normal, and increases during sexual maturation to a peak shortly before puberty.

Age Factors↗
PubMed1975

Changes in insulin content of, and insulin and RNA synthesis in, isolated rat islets of Langerhans after hypophysectomy and short-term growth hormone replacement.

Three to four weeks after hypophysectomy, the insulin content and glucose-stimulated insulin or total RNA synthesis in the pancreatic islets were estimated. The ratio of the glucose-stimulated insulin release to the islet insulin content was lowered. After short-term GH replacement, insulin release and insulin content were slightly increased such that the ratio of release to content remained virtually unaltered. Glucose-stimulated insulin synthesis was also depressed but improved slightly after GH replacement. However, there was no significant change in the incorporation of [5-3H]uridine into islet total RNA after hypophysectomy or subsequent GH replacement.

Animals↗