The effect of sex steroids on the degradation of LRH by hypothalamic homogenates

1981 ◽  
Vol 98 (3) ◽  
pp. 321-325 ◽  
Author(s):  
Anna C. Tate ◽  
A. D. Swift

Abstract. Extract of hypothalami was prepared which contained peptidase capable of degrading LRH. The degradation of LRH by this extract either alone or under the influence of oestrogens, androgens and cholesterol, when added to the extract was measured. Oestrone, oestradiol and oestriol (1 pg to 100 pg) stimulated mean peptidase activity significantly (P< 0.001) in a dose-dependent manner. Testosterone (0.1 ng to 10 ng) also caused a dose-dependent increase in degradation of LRH, the two highest doses used significantly increasing the mean activity (P < 0.001). Only the highest dose of androstenedione (10 ng) or dehydroepiandrosterone (10 ng) caused a significant increase of the mean LRH degradation (P < 0.05). Neither cholesterol nor dihydrotestosterone increased peptidase activity when added to the extract. It is suggested that it is possible that these peptidase enzymes could occupy a role in the negative feedback of steroids on the hypothalamus.

1996 ◽  
Vol 76 (01) ◽  
pp. 111-117 ◽  
Author(s):  
Yasuto Sasaki ◽  
Junji Seki ◽  
John C Giddings ◽  
Junichiro Yamamoto

SummarySodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), are known to liberate nitric oxide (NO). In this study the effects of SNP and SIN-1 on thrombus formation in rat cerebral arterioles and venules in vivo were assessed using a helium-neon (He-Ne) laser. SNP infused at doses from 10 Μg/kg/h significantly inhibited thrombus formation in a dose dependent manner. This inhibition of thrombus formation was suppressed by methylene blue. SIN-1 at a dose of 100 Μg/kg/h also demonstrated a significant antithrombotic effect. Moreover, treatment with SNP increased vessel diameter in a dose dependent manner and enhanced the mean red cell velocity measured with a fiber-optic laser-Doppler anemometer microscope (FLDAM). Blood flow, calculated from the mean red cell velocity and vessel diameters was increased significantly during infusion. In contrast, mean wall shear rates in the arterioles and venules were not changed by SNP infusion. The results indicated that SNP and SIN-1 possessed potent antithrombotic activities, whilst SNP increased cerebral blood flow without changing wall shear rate. The findings suggest that the NO released by SNP and SIN-1 may be beneficial for the treatment and protection of cerebral infarction


1989 ◽  
Vol 256 (1) ◽  
pp. R276-R280 ◽  
Author(s):  
T. Gerardo-Gettens ◽  
B. J. Moore ◽  
J. S. Stern ◽  
B. A. Horwitz

Lactation in the rat is marked by pronounced hyperphagia and suppression of brown fat (BAT) thermogenic capacity. We previously examined the possibility that elevated prolactin levels mediate these changes. The present study evaluated the effect of varying prolactin levels on food intake, BAT mitochondrial GDP binding, and carcass adiposity. Female rats were injected daily for 10 days with ovine prolactin at one of three doses: high = 3.0, medium = 1.0, or low = 0.3 micrograms/g body wt. Controls were injected with 0.9% NaCl. A group of uninjected rats served as an additional control. Cumulative food intake was significantly elevated in a dose-dependent manner in the prolactin-treated animals relative to the saline-injected and uninjected controls. Compared with the saline controls, the mean cumulative food intake was greatest at the high dose (20% increase), intermediate at the medium dose (17%), and smallest at the low dose (12%). Prolactin-treated rats gained significantly more weight during the experiment than did controls. Despite the hyperphagia in the prolactin-treated rats, no significant differences in BAT mitochondrial GDP binding were observed among the five groups. These data indicate that elevated prolactin levels stimulate food intake in a dose-dependent manner and that this hyperphagia is not accompanied by an increase in BAT mitochondrial GDP binding.


1992 ◽  
Vol 262 (2) ◽  
pp. G223-G230
Author(s):  
L. C. Knight ◽  
A. H. Maurer ◽  
R. Wikander ◽  
B. Krevsky ◽  
L. S. Malmud ◽  
...  

The aim of this study was to elucidate the effects of ethanol on gastric emptying and the trituration of solid food. With the use of a noninvasive physiological imaging technique, gastric processing of a radiolabeled solid meal was evaluated in unanesthetized dogs which ingested 6-8% ethanol solutions or received intravenous alcohol before the meal. Oral alcohol (resulting in blood levels up to 174 mg/dl) decreased the amplitude of antral contractions or completely abolished them. Alcohol did not significantly affect the fundamental frequency of contractions except at high doses, at which contractions were abolished. Alcohol lengthened the mean time to 50% of gastric emptying in a dose-dependent manner, from 132 +/- 3 min without alcohol to 160 +/- 10 min with oral alcohol at blood levels of 80-120 mg/dl (P less than 0.05). This was manifested by a lengthening of the lag phase, but there was no effect on the terminal slope of emptying (emptying rate) of the processed meal. At equal blood levels up to 120 mg/dl, orally administered alcohol had a more pronounced effect than intravenous alcohol. These data suggest that even low doses of dilute alcohol affect the ability of the antrum to process solid food and thereby contribute to impairment of gastric emptying.


1989 ◽  
Vol 256 (6) ◽  
pp. H1747-H1751 ◽  
Author(s):  
Y. Ouchi ◽  
S. Kim ◽  
A. C. Souza ◽  
S. Iijima ◽  
A. Hattori ◽  
...  

This study was conducted to investigate the effect of intracerebroventricular administration of endothelin (EDT), a novel potent vasoconstricting peptide, on blood pressure in conscious rats. The lateral cerebral ventricle of male Wistar rats was cannulated, and the femoral artery was also cannulated to measure the mean arterial blood pressure (MABP) and heart rate (HR). EDT dissolved in 10 microliters of artificial cerebrospinal fluid (ACSF) (8.25-66 pmol icv) provoked a dose-dependent increase in MABP. EDT also increased HR, although the effect of 66 pmol was variable. Intracerebroventricular ACSF did not provoke any effects on MABP and HR. Intracerebroventricular EDT also provoked contralateral rotational behavior. Pretreatment with 2 mg/kg iv phenoxybenzamine significantly suppressed the 16.5 pmol icv EDT-induced increase in MABP. Moreover, 16.5 pmol icv EDT markedly increased plasma epinephrine and norepinephrine concentration. These results indicate that EDT has a central pressor action, and the action might be mediated, at least in part, by catecholamine release to the periphery. EDT might play a role in the central control of blood pressure, although the physiological implications have not yet been determined.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Alexandra Folk ◽  
Coralia Cotoraci ◽  
Cornel Balta ◽  
Maria Suciu ◽  
Hildegard Herman ◽  
...  

Invasive fungal infection is a well-known cause of morbidity and mortality in immunocompromised patients. In this study we aimed to evaluate the hepatotoxicity induced by combined therapy of flucytosine and amphotericin B, at three different doses administered to mice for 14 days: 50 mg/kg flucytosine and 300 μg/kg amphotericin B; 100 mg/kg flucytosine and 600 μg/kg amphotericin B; 150 mg/kg flucytosine and 900 μg/kg amphotericin B. Liver injuries were evaluated by analysis of optic and electron microscopy samples, changes in TNF-α, IL-6, and NF-κB inflammation markers levels of expression, and evaluation of mRNA profiles. Histological and ultrastructural analysis revealed an increase in parenchymal and portal inflammation in mice and Kupffer cells activation. Combined antifungal treatment stimulated activation of an inflammatory pathway, demonstrated by a significant dose-dependent increase of TNF-αand IL-6 immunoreactivity, together with mRNA upregulation. Also, NF-κB was activated, as suggested by the high levels found in hepatic tissue and upregulation of target genes. Our results suggest that antifungal combined therapy exerts a synergistic inflammatory activation in a dose-dependent manner, through NF-κB pathway, which promotes an inflammatory cascade during inflammation. The use of combined antifungal therapy needs to be dose limiting due to the associated risk of liver injury, especially for those patients with hepatic dysfunction.


1990 ◽  
Vol 68 (6) ◽  
pp. 2391-2393 ◽  
Author(s):  
T. Matsuse ◽  
Y. Fukuchi ◽  
T. Suruda ◽  
T. Nagase ◽  
Y. Ouchi ◽  
...  

We examined the effect of endothelin-1 (ET-1), a novel 21-residue vasoconstrictor peptide, on pulmonary resistance (RL) in Wistar rats. The lung volume, tracheal flow, and transpulmonary pressure of tracheotomized and paralyzed rats were measured with a fluid-filled esophageal catheter and a pressure-sensitive body plethysmograph. RL was calculated by the method of von Neergaard. The femoral artery was cannulated to measure the mean arterial blood pressure. Intravenous bolus administration of synthetic ET-1 provoked a dose-dependent increase in RL in rats. The bronchoconstricting effect reached maximum at 500 pmol/kg. This bronchoconstriction was observed in less than 5 min, increased up to 15 min, and was sustained for 60 min. ET-1 increased the mean arterial blood pressure in a dose-dependent manner. We conclude that ET-1 is a hitherto unknown potent bronchoconstrictor that has a sustained effect in vivo. The potential physiological and pathophysiological role of this new peptide in the development of respiratory disease warrants further investigation.


1998 ◽  
Vol 88 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Malcolm Daniel ◽  
Richard B. Weiskopf ◽  
Mariam Noorani ◽  
Edmond I. Eger

Background Heart rate (HR) or mean arterial blood pressure (MAP) may increase in response to incision despite the absence of a motor response. The authors hypothesized that the MAC-BAR (minimum alveolar concentration of an anesthetic that blocks adrenergic response to incision) for isoflurane would exceed that for desflurane, and that fentanyl would decrease the MAC-BAR for each anesthetic in a dose-dependent manner. Methods Seventy-one patients were randomly allocated to one of six groups: desflurane or isoflurane without fentanyl or with 1.5 or 3 microg/kg fentanyl given intravenously 5 min before surgical incision. Anesthesia was induced with 2 mg/kg propofol given intravenously, and tracheal intubation facilitated with 0.1 mg/kg given intravenously. The first patient in each group received 1 MAC (end-tidal) of the inhaled anesthetic in 60% nitrous oxide (0.55 MAC), balance oxygen, maintained for at least 10 min before incision. The response was considered positive if the HR or MAP increased 15% or more. If the response was positive, the end-tidal concentration given to the next patient was 0.3 MAC greater; if the response was negative, the end-tidal concentration was 0.3 MAC less. The MAC-BAR level was calculated as the mean of four independent cross-over responses in each group. Results Desflurane and isoflurane anesthesia with 60% nitrous oxide did not change HR (P &gt; 0.05) and decreased MAP (P &lt; 0.05) before incision. Plasma epinephrine and norepinephrine concentrations after anesthesia and before incision were normal in all groups. The MAC-BAR level, without fentanyl, did not differ (P &gt; 0.05) between desflurane (1.30 +/- 0.34 MAC [mean +/- SD]) and isoflurane (1.30 +/- 0.18 MAC). Fentanyl given at 1.5 microg/kg intravenously equivalently (P &gt; 0.05) reduced the MAC-BAR for desflurane (to 0.40 +/- 0.18 MAC; P &lt; 0.05) and isoflurane (to 0.55 +/- 0.00 MAC; P &lt; 0.05), but a further increase in fentanyl to 3 microg/kg caused no greater decrease in the MAC-BAR for desflurane (0.48 +/- 0.16 MAC) and isoflurane (0.40 +/- 0.30 MAC). Conclusions Clinically attainable doses of desflurane and isoflurane, in 60% nitrous oxide (0.55 MAC), block the cardiovascular response to surgical incision at 1.3 MAC. Fentanyl given at 1.5 microg/kg decreases the MAC-BAR for each agent with no further decrease produced by 3 microg/kg fentanyl.


2010 ◽  
Vol 7 (1) ◽  
pp. 150-152 ◽  
Author(s):  
Rosemary Knapp ◽  
Edie Marsh-Matthews ◽  
Luanne Vo ◽  
Sarah Rosencrans

Sex steroids play major roles in vertebrate sexual differentiation. Unexpectedly, we now find that exposure to elevated levels of the naturally occurring stress hormone cortisol can also masculinize sexually dimorphic morphological characters and behaviour in adult female mosquitofish ( Gambusia affinis ) in a dose-dependent manner. Females masculinized by cortisol developed elongated anal fins with distal tip features similar to those of mature males. Most masculinized females also attempted to copulate when placed with normal females. Although the mechanism of masculinization is currently unknown, we propose a role for an enzyme that both inactivates cortisol and catalyzes the final step in synthesis of a major teleost androgen. This mechanism may also help explain some previously reported effects of stress on sexual development across vertebrate taxa. Our findings underscore the need to understand the full range of chemicals, both naturally occurring hormones and human-produced endocrine disruptors, that can influence sexual differentiation and reproductive function.


Author(s):  
Muhammad Y ◽  
◽  
Jatau ID ◽  

In this study, biochemical and haematological effects of kaempferol in stress induced by experimental Eimeria tenella infection in two weeks old broiler chickens was investigated. Sixty-day old broilers were randomly allotted into six groups (I-VI) of ten broilers each and brooded for two weeks with commercial broiler feed (vital feed®) and provided water ad libitum. At two weeks of age broilers in group I served as non-infected control. Broilers in groups II- VI were infected with Eimeria tenella sporulated oocyst (104/ml) via oral inoculation. After infection was established, broilers in groups II-IV were treated per os with 1 mg/kg, 1.5 mg/kg and 2 mg/kg of kaempferol respectively. Broilers in group V were treated for five days with amprolium, 1.25 g/L in drinking water. Broilers in group VI served as infected untreated control. Five days post infection; all broilers were sacrificed by severing their jugular veins. Blood sample was collected from each broiler in a plane sample container devoid of anticoagulant so as to harvest serum for serology while Ethylenediamine tetra-acetic acid (EDTA) bottles were used to collect 1 ml of blood from each bird for haematology. Concentrations of antioxidant (GPx, CAT and SOD) and liver enzymes (ALT, AST and ALP) were determined. Data obtained was analyzed using pad prism version 5.0. There were statistically significant (P<0.05) reductions in the mean values of liver enzymes (ALT, AST, ALP) in groups II, III and IV in a dose dependent manner when compared to group VI. Similarly, the mean values of antioxidant (GPx, CAT and SOD) enzymes increased significantly significant (P<0.05) in groups II, III and IV in a dose dependent manner when compared to group VI. No significant (P>0.05) difference in the mean values of antioxidants and liver enzymes were recorded between groups II, III and IV and when compared to group V. Mean Packed Cell Volume (PCV), haemoglobin (Hb) concentration and Red Blood Cell (RBC) count significantly (P<0.05) increased in groups II, III, and IV in a dose dependent manner. Similarly, PCV, Hb concentration and RBC count were significantly (P<0.05) increased in groups II, III, and IV when compared with VI. No significant (P>0.05) difference in the mean values of PCV, Hb and RBC were recorded in groups treated with kaempferol and group treated with amprolium. It was observed in this study that kaempferol improved the serum level of antioxidants and liver enzymes as well as and haematological parameters and also reduced the level of pathology in the caecum of broilers infected with Eimeria tenella in this study.


1986 ◽  
Vol 251 (2) ◽  
pp. R258-R263
Author(s):  
J. C. Lee ◽  
D. M. Denbow ◽  
M. D. Ashen ◽  
A. D. Roudabush

The purpose of this investigation was to examine the possible involvement of the central renin-angiotensin system in the pressor response to the intracerebroventricular (icv) injection of hypertonic NaCl in conscious turkeys. The icv injection was accomplished via a stereotaxically implanted stainless steel guide cannula in the lateral cerebral ventricle. The arterial blood pressure (AP) of the turkey was measured by means of a PE catheter in the left brachial artery. The icv administration of hypertonic NaCl caused a dose-dependent increase of AP. The mean AP increases due to 10-microliter icv injections of 0.9, 3.6, and 7.2% NaCl were 1.4 +/- 1.4, 18.1 +/- 3.0, and 31.2 +/- 3.2 (SE) mmHg, respectively. These changes were statistically significant (P less than 0.001). The icv administration of captopril, [Sar1, Ile8]angiotensin II, or pentobarbital sodium markedly reduced the pressor response to the icv injection of hypertonic 7.2% NaCl. Blockade of central adrenergic receptors with phentolamine and propranolol was without effect. These results support the contention that the central renin-angiotensin system may directly contribute to pressor responses induced by central hypertonic NaCl stimulation.


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