Effect Of Hypophysectomy Research Articles

Sex-specific responses to growth hormone and luteinizing hormone in a model teleost, the Mozambique tilapia

Across the vertebrate lineage, sexual dimorphism in body size is a common phenomenon that results from trade-offs between growth and reproduction. To address how key hormones that regulate growth and reproduction interact in teleost fishes, we studied Mozambique tilapia (Oreochromis mossambicus) to determine whether the activities of luteinizing hormone (Lh) are modulated by growth hormone (Gh), and conversely, whether targets of Gh are affected by the presence of Lh. In particular, we examined how gonadal morphology and specific gene transcripts responded to ovine GH (oGH) and/or LH (oLH) in hypophysectomized male and female tilapia. Hypophysectomized females exhibited a diminished gonadosomatic index (GSI) concomitant with ovarian follicular atresia. The combination of oGH and oLH restored GSI and ovarian morphology to conditions observed in sham-operated controls. A similar pattern was observed for GSI in males. In control fish, gonadal gh receptor (ghr2) and estrogen receptor β (erβ) expression was higher in females versus males. A combination of oGH and oLH restored erβ and arβ in females. In males, testicular insulin-like growth factor 3 (igf3) expression was reduced following hypophysectomy and subsequently restored to control levels by either oGH or oLH. By contrast, the combination of both hormones was required to recover ovarian igf3 expression in females. In muscle, ghr2 expression was more responsive to oGH in males versus females. In the liver of hypophysectomized males, igf2 expression was diminished by both oGH and oLH; there was no effect of hypophysectomy, oGH, or oLH on igf2 expression in females. Collectively, our results indicate that gene transcripts associated with growth and reproduction exhibit sex-specific responses to oGH and oLH. These responses reflect, at least in part, how hormones mediate trade-offs between growth and reproduction, and thus sexual dimorphism, in teleost fishes.

Functional Pituitary Tumors Masquerading as Primary Glaucoma and Effect of Hypophysectomy on Intraocular Tension

We report 2 bilateral cases that presented as primary ocular hypertension and primary angle-closure glaucoma, respectively; however, they were subsequently discovered to be harboring secretory pituitary tumors. After transsphenoidal tumor resection, intraocular pressures (IOPs) in all 4 eyes returned to normal levels. Sudden rise in IOP then again served as a primary manifestation of relapse in the second patient with growth hormone secreting pituitary tumor. It was not found feasible for resurgery; thus, patient needed trabeculectomy in both eyes to achieve an optimum control of intraocular tension. We conclude that pituitary adenomas may mimic primary glaucoma without producing vertical hemianopia and cause a reversible rise in IOP. Furthermore, a careful ongoing expert ophthalmologic assessment may serve as a useful clinical marker for early relapse in these tumors.

Seymour Van Meter, the 2008 Van Meter Prize Award Review, and Philip E. Smith's Early Publication on the Effects of Hypophysectomy in the OrderAnura

Seymour Van Meter, the 2008 Van Meter Prize Award Review, and Philip E. Smith's Early Publication on the Effects of Hypophysectomy in the Order<i>Anura</i>

Effects of Hypophysectomy on Pro-Thyrotropin-Releasing Hormone Concentrations in Rats

The effects of hypophysectomy on pro-thyrotropin-releasing hormone (pro-TRH) and TRH concentrations in the rat hypothalamus, cerebrum, cerebellum and brain stem, stomach and eye were studied. The hypophysectomy was performed via ear route and the rats were used for experiments at seven days after the operation. The hypophysectomized rats were administered T4 (500 micrograms/kg), T3 (100 micrograms/kg), TRH (1.0 mg/kg), or bovine TSH (1.25 IU/kg) was injected ip, and five rats in each subgroup were decapitated at four hours after the injection. Pro-TRH, TRH, TSH and thyroid hormone were measured by their radioimmunoassays. Immunoreactive pro-TRH (ir-pro-TRH) concentrations in the hypothalamus increased significantly after hypophysectomy, while its concentrations in the other tissues showed no changes. The immunoreactive TRH (ir-TRH) concentrations in the hypothalamus decreased significantly after hypophysectomy, but its concentrations did not change in the other tissues. In the hypophysectomized rats, ir-pro-TRH concentrations in the hypothalamus decreased significantly after T4 or T3 injection and tended to decrease after TRH or TSH injection. The ir-TRH concentrations in the hypothalamus increased significantly after T4, T3, TSH or TRH injection in the hypophysectomized rats. However, ir-pro-TRH and ir-TRH concentrations in the other tissues did not change after these hormone injections. The findings suggest that hypophysectomy stimulates TRH synthesis and release in the hypothalamus, and that pro-TRH synthesis in the tissues except the hypothalamus may not be regulated with thyroid hormone.

Effects of hypophysectomy on compulsive checking and cortical dendrites in an animal model of obsessive-compulsive disorder

Hormones may modulate the symptoms of obsessive-compulsive disorder (OCD), but the evidence is equivocal and not consistent across studies, with findings of hormone-associated increases and decreases of symptoms. To assess whether a strong endocrine influence on OCD exists, the effects of hypophysectomy were examined in an animal model of OCD. The model involves repeated injections of the dopamine D2/D3 receptor agonist, quinpirole, to induce locomotor sensitization and compulsive checking behavior. Intact and hypophysectomized rats were administered quinpirole (0.5 mg/kg x 6, twice weekly) or saline and compulsive checking in a large open field was measured according to a standard protocol. Results showed that in hypophysectomized animals, the development of locomotor sensitization was attenuated but the expression of quinpirole-induced compulsive checking was full-blown. Analysis of Golgi-stained neurons showed changes in spine density in Cg3 and Par1 and increased branching of apical dendrites in Cg3. It is suggested that compulsive checking could be coupled with drug-induced increases in Cg3 dendritic branching and that changes in spine density may reflect a compensatory adjustment in dopamine-innervated regions. On the basis of the animal model findings, it is concluded that the presence of OCD checking compulsions is not dependent on pituitary axis hormones.

Seymour D. Van Meter, M.D. (1865–1934): The Texan Who Wielded a Scalpel in Denver and Left a Lasting Legacy

ThyroidVol. 17, No. 8 Thyroid HistorySeymour D. Van Meter, M.D. (1865–1934): The Texan Who Wielded a Scalpel in Denver and Left a Lasting LegacyJames A. MagnerJames A. MagnerSearch for more papers by this authorPublished Online:29 Aug 2007https://doi.org/10.1089/thy.2007.0141AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byWhy the History of Thyroid Disease Is Important4 September 2009 | Thyroid, Vol. 19, No. 9Seymour Van Meter, the 2008 Van Meter Prize Award Review, and Philip E. Smith's Early Publication on the Effects of Hypophysectomy in the Order Anura4 September 2009 | Thyroid, Vol. 19, No. 9 Volume 17Issue 8Aug 2007 InformationCopyright 2007, Mary Ann Liebert, Inc.To cite this article:James A. Magner.Seymour D. Van Meter, M.D. (1865–1934): The Texan Who Wielded a Scalpel in Denver and Left a Lasting Legacy.Thyroid.Aug 2007.779-785.http://doi.org/10.1089/thy.2007.0141Published in Volume: 17 Issue 8: August 29, 2007Online Ahead of Print:July 24, 2007PDF download

The effect of hypophysectomy on the cortisol secretion in 4 patients with advanced metastatic breast cancer.

Abstract A raised cortisol production rate is found in patients with advanced breast cancer. The cortisol production rate was estimated before and after hypophysectomy in 4 patients with metastatic disease and was found to fall to one-sixth of the original level. It is concluded that the high preoperative cortisol production rate was dependent on pituitary function and was not due to the production of corticotrophin by the tumour cells.

Pituitary control of cholesterol metabolism in normal and LDL receptor knock-out mice: Effects of hypophysectomy and growth hormone treatment

The pituitary is important in the control of lipid metabolism and studies of hypophysectomized (Hx) rats have shown strong effects of growth hormone (GH) on bile acid synthesis, hepatic LDL receptor (LDLR) expression and on the sensitivity to dietary cholesterol. It is unclear if mice may be used in such studies. The aim of the current study was to evaluate if Hx mice may be used to further explore how GH modulates cholesterol and bile acid metabolism, and to define the importance of the LDLR in this regulation by studying LDLR-deficient mice (LDLRko). Experiments on three mouse strains showed that, following Hx, HDL were reduced and LDL increased. Cholesterol/fat feeding of Hx mice increased serum cholesterol levels 2- to 3-fold. Serum triglycerides were reduced 50% in Hx mice; a further 30% reduction was seen after dietary cholesterol/fat. A serum marker for CYP7A1-mediated bile acid synthesis (C4) increased 2-fold in intact mice on cholesterol/fat diet. In Hx mice C4 levels were reduced by 50% as compared to intact controls, but were unexpectedly increased to levels seen in normal mice upon cholesterol/fat feeding. Hx of LDLRko mice moderately increased LDL-cholesterol and reduced triglycerides and GH treatment attenuated these effects; serum C4 levels were increased by GH treatment in all groups. In conclusion, mice can be used to explore the role of the pituitary in lipid metabolism. CYP7A1 is generally reduced in Hx mice but has a normal stimulatory response following dietary cholesterol suggesting that faulty regulation of CYP7A1 is not important for the reduced resistance to dietary cholesterol in Hx mice. Further, the LDLR is only to a minor part involved in the pituitary regulation of serum cholesterol in mice.

Effect of Hypophysectomy and Growth Hormone Administration on Myosin Heavy Chains in Rat Skeletal Muscle

Effect of Hypophysectomy and Growth Hormone Administration on Myosin Heavy Chains in Rat Skeletal Muscle

Effect of Hypophysectomy and Growth Hormone Administration on Myosin Heavy Chains in Rat Skeletal Muscle

Effect of Hypophysectomy and Growth Hormone Administration on Myosin Heavy Chains in Rat Skeletal Muscle

Effects on extrahepatic UDP-glucuronosyltransferases in hypophysectomized rat.

The effects of hypophysectomy on hepatic and extrahepatic UDP-glucuronosyltransferase activities in adult male rats were observed. UDP-glucuronosyltransferase activities toward 1-naphthol decreased to 20-30% of control in the liver, kidney, lung, and testis. The mRNA of UGT1A6, which is an isoform contributing to the glucuronidation of various phenolic xenobiotics such as 1-naphthol, were decreased drastically in the liver, kidney, and testis by hypophysectomy. However, while bilirubin UDP-glucuronosyltransferase activity in the liver intensified, there was only a slight increase in the activity in the kidney and no alteration in the lung. The mRNA of UGT1A1, which is an isoform contributing to the glucuronidation of bilirubin, increased significantly in the liver and slightly in the kidney after hypophysectomy. These inductions and reductions in enzymatic activities and mRNA levels in each tissue were restored to control levels by intermittent injections of rat growth hormone. Interestingly, while hepatic UGT activity toward bisphenol A remained constant in hypophysectomized rats, the testicular UGT activity declined to 10-15% of control but returned to normal levels following growth hormone treatment, suggesting that an unknown UGT isoform (s) mediates bisphenol A glucuronidation in the testis. These results indicate that the expression of extrahepatic UGT is isoform-specific and regulated differentially in tissues by the pituitary gland.

Vaginocervical Stimulation Releases Oxytocin within the Spinal Cord in Rats

Vaginocervical stimulation (VS) significantly elevated the concentration of oxytocin (OT) in spinal cord superfusates of 8 intact urethane-anesthetized rats measured 10–15 min after VS (median [interquartile range]: 1.7 [1.00–3.37] pg/ml) compared to that measured 10–15 min before VS (1.1 [1.01–1.40] pg/ml). When VS was administered once (n = 8), it produced a 55% increase over baseline values; when administered a second time 45 min later (n = 6), it produced only a 22% increase over pre-VS values. The effects of estrogen on the VS-induced release of OT were then investigated using ovariectomized rats that were treated either with estradiol benzoate (EB; 10 µg/100 g bw) (n = 6) or with an oil vehicle (n = 6) subcutaneously for 3 days. The EB treatment significantly elevated the basal levels of OT released into spinal cord superfusates above vehicle control levels. Within 5–10 min after the onset of VS, OT concentrations in the superfusates were significantly higher in EB-treated than in vehicle-treated rats. The vehicle-treated rats did not show a significant elevation in OT concentration following VS. To rule out the possibility that the posterior pituitary gland was the source of this OT, the effect of hypophysectomy (HYPOX) was assessed on the VS-induced release of OT into spinal cord superfusates and plasma. The concentration of OT in spinal cord superfusates of both the HYPOX (n = 5) and intact rats (n = 6) increased significantly from 5.8 [4.4–6.5] pg/ml pre-VS to 7.9 [6.7–10.3] pg/ml immediately after VS, and from 4.4 [3.8–5] pg/ml pre-VS to 5.1 [4.6–5.7] pg/ml immediately after VS, respectively. There was no significant difference in baseline levels of OT in cerebrospinal fluid between the two groups. By contrast, plasma OT levels, while significantly elevated in response to VS from 3.42 [2.9–5.34] pg/ml baseline to 7.25 [5.33–15.77] pg/ml in the intact group, failed to respond significantly to VS in the HYPOX group (n = 5). The present findings provide evidence of a direct estrogen-dependent release of OT within the spinal cord in response to VS, presumably via descending oxytocinergic neurons.

Hypophysectomy depresses immune functions in rainbow trout

As the immune system is known to be influenced by the endocrine system, the effects of hypophysectomy on immune functions were examined in the rainbow trout ( Oncorhynchus mykiss). Superoxide anion (O 2 −) production, accompanied by phagocytosis, was significantly decreased in leucocytes isolated from the head kidney 7 days after hypophysectomy. Significant reduction was also observed in plasma immunoglobulin (Ig) M levels, whereas no change was observed in plasma lysozyme activity. The number of Ig-secreting leucocytes in peripheral blood had decreased after hypophysectomy, although total leucocyte number was not affected. The percentage of Ig-producing leucocytes as assessed by flow cytometry using a monoclonal antibody to trout IgM showed significant reduction in the head kidney. However, hypophysectomy did not affect the number of Ig-producing leucocytes in spleen, thymus or peripheral blood. By RT-PCR, expression of two growth hormones (GH I and II) and prolactin (PRL) mRNA was detected in lymphoid tissues, such as head kidney, spleen, thymus and intestine, as well as in leucocytes from blood and head kidney, indicating the local production of these hormones. These results indicate important roles of hypophyseal hormones produced not only in the pituitary, but also in the lymphoid tissues, in the maintenance of the immune functions in trout.

Microarray Analysis of the in Vivo Effects of Hypophysectomy and Growth Hormone Treatment on Gene Expression in the Rat

Microarray Analysis of the in Vivo Effects of Hypophysectomy and Growth Hormone Treatment on Gene Expression in the Rat

Effect of Hypophysectomy and Growth Hormone Replacement on the Modulation of P450 Expression after Treatment with the Aromatic Hydrocarbon Ethylbenzene

Pituitary status has a significant effect on the expression of several cytochrome P450 enzymes. The goal of this study was to examine the role of pituitary input on the modulation of CYP2C11 and CYP2B after treatment with the aromatic hydrocarbon ethylbenzene (EB). Intact, hypophysectomized (HX), and HX rats supplemented with pulsatile growth hormone (GH) were treated with corn oil or EB and the effects on hepatic P450 expression were determined. Hypophysectomy caused a 50% decrease in CYP2C11 protein in untreated rats, whereas GH supplementation returned protein to control levels. EB administration also decreased CYP2C11 protein in intact rats; however, this decrease was not observed after EB treatment in HX or HX + GH groups. CYP2C11-dependent testosterone 2α-hydroxylation followed a similar pattern as CYP2C11 protein, except that the activity was only partially restored by GH replacement. CYP2B levels were also substantially influenced by hypophysectomy. Intact rats exhibited a 100-fold increase in CYP2B1 mRNA, reaching a maximum 12 h after EB administration. A much smaller response (ca. 20-fold) was observed in HX rats, reaching a maximum 24 h after EB treatment. This effect was not reversed by GH supplementation. The half-life for EB was significantly increased from 8 h in intact rats to 14 h in HX rats, suggesting higher plasma EB concentrations after EB administration to HX rats. These results indicate that CYP2C11 and CYP2B become less responsive to EB-dependent modulation in HX rats, a response that cannot be explained simply by absence of GH or by altered EB pharmacokinetics in HX animals.

Triiodothyronine downregulates the periportal expression of α class glutathione S-transferase in rat liver

Most drug-metabolizing phase I and phase II enzymes, including the glutathione S-transferases (GST), exhibit a zonated expression in the liver, with lower expression in the upstream, periportal region. To elucidate the involvement of pituitary-dependent hormones in this zonation, the effect of hypophysectomy and 3,3′,5-triiodo- L-thyronine (T 3) on the distribution of GST was studied in rats. Hypophysectomy increased total GST activity both in the periportal and perivenous liver region. Subsequent T 3 treatment counteracted this effect in the perivenous zone. However, analysis for either μ class M1/M2-specific (1,2-dichloro-4-nitrobenzene) or α class A1/A2-specific (7-chloro-4-nitrobenzo-2-oxa-1,3-diazole) GST activity revealed that T 3 treatment did not significantly affect the perivenous activity of these GST classes. In contrast, T 3 was found to significantly counteract the increase of α class GST activity caused by hypophysectomy in the periportal zone. To establish whether this effect was T 3-specific, hepatocytes were isolated from either the periportal and perivenous zone by digitonin/collagenase perfusion and cultured either as pyruvate-supplemented monolayer or as co-culture with rat liver epithelial cells. Only in the latter it was found that T 3 suppressed the A1/A2-specific GST activity and α class proteins predominantly in periportal cells. The data demonstrate that T 3 is an important factor responsible for the low expression of α GST in the periportal region. T 3 may be involved in the periportal downregulation of other phase I and II enzymes as well.

Role of glucose utilization in the restoration of hypophysectomy-induced hepatic cytochrome P450 2E1 by growth hormone in rats

Growth hormone and insulin are the primary determinants for cytochrome P450 2E1 (CYP2E1) expression. The role of glucose on the induction of CYP2E1 by hypophysectomy and on the restorative effect by growth hormone was investigated in the rat liver. Western and Northern blot analyses revealed that hypophysectomy induced CYP2E1 by 5-fold at 1–4 weeks, relative to control, with a concomitant increase in CYP2E1 mRNA. Hypophysectomized rats (HXR) showed a 20% reduction in the plasma glucose level. Hypophysectomy-induced increase in the CYP2E1 mRNA was completely abolished by glucose feeding in drinking water (10%) for 7 days. Treatment of HXR with hGH (2 I.U./kg, twice a day, for 7 days) inhibited the increases in CYP2E1 protein and mRNA levels with restoration of the plasma glucose level. In contrast to the effect of human growth hormone (hGH) on CYP2E1 in HXR with free access to foods, CYP2E1 expression failed to be restored by hGH in starving HXR. However, glucose feeding of starving HXR abolished the induction of CYP2E1. Effects of hypophysectomy and hGH treatment were studied in streptozotocin-induced diabetic rats. Insulin, but not hGH, prevented an increase in CYP2E1 mRNA in diabetic rats. The hepatic CYP2E1 induction in hypophysectomized diabetic rats was inhibited by hGH treatment, indicating that the hGH effect on CYP2E1 expression did not involve insulin production. These results provide evidence that the induction of hepatic CYP2E1 by hypophysectomy may result from reduced glucose utilization, and that the effect of hGH on CYP2E1 expression may be mediated with enhanced glucose utilization, but not with insulin production.

Hypophysectomy Results in a Loss of Connexin Gap Junction Protein from the Adrenal Cortex

To test the hypothesis that gap junctions are dependent on the tropic state of the adrenal gland, the effect of hypophysectomy on connexin 43 (α1-Cx43) gap junction protein occurrence and distribution was examined in mice. Gap junction protein occurrence was assessed with immunohistochemical techniques. In the adrenal gland from intact animals, α1- Cx43 gap junction protein was detected in the zonae fasciculata(ZF) and reticularis (ZR) while only a few α1- Cx43 gap junction plaques were found connecting zona glomerulosa(ZG) cells. Hypophysectomy led to a profound atrophy of the cortex which was more marked in the inner zones (zonae fasciculata and reticularis) than in the zona glomerulosa. There was a time dependent loss of α1- Cx43 gap junction protein in the adrenal cortex after hypophysectomy. At 33 day following hypophysectomy there was a two fold decrease in gap junctions in the zona fasciculata while the average gap junction plaque size was not different than the size seen in control animal adrenal glands. ACTH (lU/gm body weight) treatment in hypophysectomized animals increased the number of gap junction plaques in the zona fasciculata. Hypophysectomy led to diminished α1-Cx43 gap junction expression in the zona fasciculata which could be restored by ACTH treatment. Because altering the tropic state of the adrenal glands via hypophysectomy leads to a reduction in gap junction number, it can be suggested that control of gap junction expression in the adrenal gland is hormone dependent and linked to adrenal gland function.

Seasonal variations in sperm production and sperm quality in male winter flounder, Pleuronectes americanus : the effects of hypophysectomy, pituitary replacement therapy, and GnRH-A treatment

The pattern of sperm release and changes in sperm quality were investigated throughout the normal spawning season of male winter flounder, Pleuronectes americanus (Walbaum), caught in Conception Bay, Newfoundland, Canada in April and November 1994. In addition, the impact of hormonal manipulation on sperm production and sperm quality was examined through gonadotropin-releasing hormone analogue (GnRH-A) treatment, hypophysectomy, and pituitary extract injection – pituitary replacement therapy (PRT). While a lengthy period of spermiation, lasting ∼6 months (December to July), can be detected in some males, the major period for sperm release occurred in May to July in the summer spawning season. The spawning period started with peak levels of plasma testosterone (T) and 11 ketotestosterone (11-KT). By late July sperm production fell rapidly along with a notable deterioration in sperm motility. While GnRH-A treatment advanced the period of sperm release, and the milt became diluted and increased in volume, the treatment did not increase total sperm output over the spawning season. In hypophysectomized male flounder, by contrast, milt was more concentrated and sperm production declined along with reduced plasma androgen levels during the spawning season. Increased plasma T and 11-KT levels in hypophysectomized males followed PRT in December and January. Moreover, PRT appeared to be responsible for advancement of spermiation in a large number of prespawning males, which released an increased amount of milt. Finally, these studies indicated that both sperm motility and egg fertilization rates remained unchanged after these hormonal treatments.

Glucocorticoids differentially control synthesis of acetylcholinesterase and butyrylcholinesterase in rat liver and brain

Mammalian organisms posses two cholinesterases: acetylcholinesterase (AChE, EC 3.1.1.7.) and butyrylcholinesterase (BuChE, EC 3.1.1.8.). A clear explanation for this dual expression of acetylcholine-hydrolyzing enzymes is still missing. Better knowledge on how these two enzymes respond to various physiological or pharmacological factors would importantly contribute to the understanding of their function. The aim of the present study is to elucidate glucocorticoid (GC) influences on the synthesis of AChE and BuChE in rat liver and brain. Female Wistar rats were treated with dexamethasone until body weight loss was greater than 15%, signaling full expression of a GC response. At this stage, liver and brain were isolated and AChE and BuChE activities were determined in their homogenates. A new approach, based on precise radiometric measurements of AChE and BuChE activities in the polysomal fractions, prepared under non-denaturing conditions, was used to study GC influences on the early stages of biosynthesis of both enzymes. We found a differential GC influence on AChE and BuChE. In brain, only BuChE activity was affected (−30%), while AChE remained practically unchanged. In liver, BuChE activity fell by 60%, while AChE lost only 18% of its control activity. In case of BuChE, decreased activities in the whole homogenates correlated with decreased activities in the polysomal fractions, suggesting that early stages of enzyme biosynthesis were primarily affected. On the other hand, decreased AChE activity in liver homogenates was not paralleled by a significant change at the level of polysomal AChE activity in this organ, suggesting that higher AChE turn-over is primarily responsible for the decreased activity in homogenate. These results, together with the GC-mediated elimination of the correlation between brain and liver BuChE activities, strongly support the proposal of Edwards and Brimijoin (J.A. Edwards, S. Brimijoin, Effects of hypophysectomy on acetylcholinesterase and butyrylcholinesterase in the rat, Biochem. Pharmacol. 32 (1983) 1183–1189) that BuChE is regulated by systemically acting factors, including various hormones, while regulation of AChE is primarily tissue-specific.