Effects of long- and short-term gonadectomy on the hypothalamo-hypophysial (LH-releasing hormone–LH) system in oestrogen-treated male and female rats

1986 ◽  
Vol 110 (2) ◽  
pp. 367-373 ◽  
Author(s):  
N. G. Weiland ◽  
C. A. Barraclough ◽  
K. J. Catt

ABSTRACT Considerable differences have previously been found in the hypothalamo-hypophysial responsiveness to oestrogen, depending upon the time between gonad removal and exposure to oestrogen. In the present study a detailed analysis was made of some of the differences which may exist in pituitary LH-releasing hormone (LHRH) receptors and the amount of LH released in response to electrochemical depolarization of the medial preoptic area after 2 or 7 days of oestradiol treatment of long- and short-term gonadectomized male and female rats. The pituitary glands of long-term gonadectomized males and females secreted more LH in response to two pulse injections of LHRH than did short-term gonadectomized rats. The amount of LH released on day 2, however, was equivalent to that secreted after 7 days of oestradiol treatment. Moreover, long-term gonadectomized males and females had equivalent LHRH receptor concentrations, which were greater than those of short-term gonadectomized animals. Peak serum LH concentrations observed after preoptic stimulation were equivalent in short- and long-term castrated rats after 2 days of oestrogen exposure. Serum LH concentrations following preoptic stimulation in short-term gonadectomized males and females were significantly greater on day 7 than on day 2 of oestradiol treatment, whereas in long-term gonadectomized animals the stimulated release of LH was equivalent both in magnitude and time of peak release on both days. These studies demonstrate that the differential effects of oestradiol on LH release on day 2 (no negative feedback) compared with day 7 (both negative and positive feedback exist) are not due to differences in the ability of the pituitary gland to release LH in response to LHRH, nor in the releasable pools of hypothalamic LHRH in long-term gonadectomized rats. Rather, they seem to be due to a refractoriness in some unidentified central nervous process which regulates tonic LH release in gonadectomized rats. J. Endocr. (1986) 110, 367–373

1994 ◽  
Vol 76 (4) ◽  
pp. 1540-1547 ◽  
Author(s):  
D. J. Prezant ◽  
B. Richner ◽  
T. K. Aldrich ◽  
D. E. Valentine ◽  
E. I. Gentry ◽  
...  

The effects of long-term undernutrition (10 wk) on diaphragm contractility, fatigue, and fiber type proportions were studied in male and female rats. Contractility and fatigue resistance indexes were measured in an in vitro diaphragm costal strip preparation by using direct stimulation at 37 degrees C. Undernutrition allowed for continued growth in males and females but with substantial reductions in weight gain. Relative to control rats of the same sex, final weights were significantly lower in undernourished males (74 +/- 3%) than females (90 +/- 5%), but weight gain was not significantly different between undernourished males (58 +/- 5%) and females (60 +/- 3%). Only in males did undernutrition significantly reduce costal diaphragm weight (to 77 +/- 5% of control). Diaphragm forces, normalized for cross-sectional area, were not significantly different from male or female control values. Fatigue resistance indexes (fatigue/baseline force) were increased at all stimulation frequencies in undernourished males but not in undernourished females. Costal diaphragm atrophy, involving types I and II fibers, occurred in undernourished males but not in undernourished females. In conclusion, despite long-term undernutrition reducing weight gain to similar levels in males and females (relative to control), there was excellent preservation of diaphragm weight, function, and structure in females but, although diaphragm atrophy occurred, there was preserved contractility and increased fatigue resistance in males.


Author(s):  
Xiaomeng Qiao ◽  
Mizhu Sun ◽  
Yuanyuan Chen ◽  
Wenyang Jin ◽  
Huan Zhao ◽  
...  

Abstract Aims Ethanol ingestion affects cognition and emotion, which have been attributed to the dysfunction of specific brain structures. Studies of alcoholic patients and animal models consistently identify reduced hippocampal mass as a key ethanol-induced brain adaptation. This study evaluated how neuroadaptation in the hippocampus (Hip) produced by ethanol contributed to related behavioral deficits in male and female rats. Methods Effects of acute, short-term and long-term ethanol exposure on the anxiety-like behavior and recognition memory on adult male and female Sprague–Dawley rats were assessed using elevated plus maze test and novel object recognition test, respectively. In addition, in order to investigate the direct effect of ethanol on hippocampal neurons, primary culture of hippocampal neurons was exposed to ethanol (10, 30 and 90 mM; 1, 24 and 48 h), and viability (CCK-8) and morphology (immunocytochemistry) were analyzed at structural levels. Western blot assays were used to assess protein levels of NT3-TrkC-ERK. Results Acute and short-term ethanol exposure exerted anxiolytic effects, whereas long-term ethanol exposure induced anxiogenic responses in both sexes. Short-term ethanol exposure impaired spatial memory only in female rats, whereas long-term ethanol exposure impaired spatial and recognition memory in both sexes. These behavioral impairments and ethanol-induced loss of hippocampal neurons and decreased cell viability were accompanied by downregulated NT3-TrkC-ERK pathway. Conclusion These results indicate that NT3-TrkC-ERK signaling in the Hip may play an important role in ethanol-induced structural and behavioral impairments.


1988 ◽  
Vol 119 (1) ◽  
pp. 15-21 ◽  
Author(s):  
O. F. X. Almeida ◽  
K. E. Nikolarakis ◽  
A. Herz

ABSTRACT The control of LHRH and LH by neurotransmitters and neuromodulators such as the endogenous opioid peptides is essentially the same in intact adult male and female rats: adrenergic and dopaminergic agonists stimulate LH release and opioid agonists inhibit it. Several weeks after gonadectomy, however, the contribution of the endogenous ligands of adrenergic, dopaminergic and opioidergic receptors to the control of LHRH is altered. A detailed pharmacological analysis in long-term ovariectomized females confirmed previous reports that adrenergic and dopaminergic agonists still enhance secretion of LHRH and LH and opioid receptor agonists still suppress it. A similar investigation in long-term castrated males also confirmed previous reports that opioid agonists fail to block LH secretion. In addition, we have found that while adrenergic and dopaminergic agonists cause increases in serum concentrations of LH, adrenoreceptor and dopamine receptor antagonists do not inhibit LH release in long-term castrates. Furthermore, the opioid antagonist naloxone does not raise serum LH levels in either sex after long-term gonadectomy. These observations therefore imply reduced opioidergic, dopaminergic and adrenergic transmission, in relation to LHRH release, after longterm castration. In addition, opioid receptor activity (assessed by responsiveness to an opioid receptor agonist) of female rats is maintained, whereas that of male rats is lost, after long-term gonadectomy. J. Endocr. (1988) 119, 15–21


1981 ◽  
Vol 97 (2) ◽  
pp. 181-185 ◽  
Author(s):  
Daniel M. Linkie ◽  
Jacob Furth ◽  
Diane Kourelakos

Abstract. The patterns of gonadotrophin secretion in intact controls and in male and female rats castrated for up to 36 months were established utilizing specific radioimmunoassay methods. Plasma LH increased 14– 16-fold and FSH rose 4–8-fold in rats of either sex in the first 30 days following gonadectomy. The subsequent 30 day interval showed an additional 76% increase of LH in both sexes and increases in FSH of 32 and 61% in males and females, respectively. These levels were maintained for an additional 34 months. The number of hypophyseal gonadotrophin containing cells, studied by immunohistochemical localization techniques, increased following gonad removal in a pattern similar to that for the circulating hormones. Development of gonadotrophin secreting tumours did not correlate with plasma gonadotrophin concentrations which suggests that the gonadotropes are uniquely resistant to tumourogenesis unlike mammotropes, thyrotropes, and corticotropes.


1993 ◽  
Vol 75 (3) ◽  
pp. 1140-1149 ◽  
Author(s):  
D. J. Prezant ◽  
D. E. Valentine ◽  
E. I. Gentry ◽  
B. Richner ◽  
J. Cahill ◽  
...  

The effects of short-term (2.5 wk) and long-term (10 wk) testosterone propionate (2.5 mg/day; 5 days/wk) treatment on diaphragm contractility, fatigue resistance, and fiber type proportions were studied in male and female rats. Contractility and fatigue resistance indexes were measured in an in vitro diaphragm costal strip preparation by direct stimulation at 37 degrees C. The fatigue paradigm consisted of 30 trains/min at 5 Hz (50% duty cycle) for 10 min. Fatigue resistance indexes were calculated as postfatigue divided by baseline forces. In females but not males, testosterone treatment produced significant increases in body weight, costal diaphragm weight, and contractility and significant decreases in fatigue resistance indexes. The interaction between testosterone treatment and the duration of treatment was significant, with the increase in contractility (females) being significant after short-term but not long-term treatment. No significant difference in fiber type proportions or areas was observed, regardless of treatment duration or the preexperimental, basal circulating level of androgen.


Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Omeed Rahimi ◽  
Jay L Kirby ◽  
Jasmina Varagic ◽  
E. Ann Tallant ◽  
Patricia E Gallagher

Doxorubicin (Dox), a commonly used and effective chemotherapeutic agent, often produces cumulative dose-dependent cardiovascular toxicity, resulting in long-term hypertrophy and fibrosis which can lead to heart failure. Adjunct therapies are thus needed to reduce Dox-induced cardiovascular toxicity and enhance long-term quality-of-life in cancer patients, especially in pediatric patients. Angiotensin-(1-7) [Ang-(1-7)] is an endogenous peptide hormone of the renin-angiotensin system that improves cardiac and vascular function by reducing hypertrophy and fibrosis in various animal models. In this study, juvenile Sprague-Dawley rats (male and female, n = 8-10) were administered Dox (cumulative dose of 22 mg/kg) for 6 week, in the presence and absence of Ang-(1-7) [24 μg/kg/h]. Aortic function was measured using a Vevo 2100 small animal ultrasound system. In both males and females, Dox administration increased pulse wave velocity (PWV), a measure of arterial stiffness, and co-treatment with Ang-(1-7) attenuated the Dox-induced increase (Males - 5.6 ± 0.5, Sham; 9.7 ± 1.4, Dox; 7.8 ± 0.6 m/s, Dox/Ang-(1-7), p < 0.01; Females - 5.1 ± 0.5, Sham; 14.3 ± 1.5, Dox; 7.7 ± 1.2 m/s, Dox/Ang-(1-7), p < 0.001); Ang-(1-7) alone had no effect. Dox increased aortic thickness and decreased aortic diameter at systole in males only, which was attenuated by Ang-(1-7) (aortic thickness - 0.28 ± 0.01, Sham; 0.33 ± 0.01, Dox; 0.28 ± 0.01 mm, Dox/Ang-(1-7), p < 0.01; aortic diameter - 2.8 ± 0.6, Sham; 2.3 ± 0.1, Dox; 2.5 ± 0.1 mm, Dox/Ang-(1-7); p < 0.01). No change in aortic thickness or diameter was observed following treatment with Ang-(1-7) alone. Conversely, Dox increased fibrosis in female aorta only, measured by immunohistochemistry with Picrosirius red, which was attenuated by Ang-(1-7) (5.4 ± 0.3, Sham; 7.2 ± 0.6, Ang-(1-7); 12.8 ± 2.0, Dox; 8.0 ± 1.0%, Dox/Ang-(1-7); p < 0.001). These results demonstrate that Dox causes aortic dysfunction in both males and females, albeit through different mechanisms—an increase in aortic hypertrophy in males and aortic fibrosis in females. Ang-(1-7) attenuated both the hypertrophy and fibrosis, suggesting that treatment with the heptapeptide hormone may serve as an effective adjuvant to improve Dox-induced aortic dysfunction.


1968 ◽  
Vol 58 (4) ◽  
pp. 600-612 ◽  
Author(s):  
Robert Boyd ◽  
Donald C. Johnson

ABSTRACT The effects of various doses of testosterone propionate (TP) upon the release of luteinizing hormone (LH or ICSH) from the hypophysis of a gonadectomized male or female rat were compared. Prostate weight in hypophysectomized male parabiotic partners was used to evaluate the quantity of circulating LH. Hypophyseal LH was measured by the ovarian ascorbic acid depletion method. Males castrated when 45 days old secreted significantly more LH and had three times the amount of pituitary LH as ovariectomized females. Administration of 25 μg TP daily reduced the amount of LH in the plasma, and increased the amount in the pituitary gland, in both sexes. Treatment with 50 μg caused a further reduction in plasma LH in males, but not in females, while pituitary levels in both were equal to that of their respective controls. LH fell to the same low level in partners of males or females receiving 100 μg TP. When gonadectomized at 39 days, males and females had the same amount of plasma LH, but males had more stored hormone. Pituitary levels were unchanged from controls following treatment with 12.5, 25 or 50 μg TP daily, but plasma values dropped an equal amount in both sexes with the latter two doses. Androgenized males or females, gonadectomized when 39 days old, were very sensitive to the effects of TP and plasma LH was significantly reduced with 12.5 μg daily. Pituitary LH in androgenized males was higher than that of normal males but was reduced to normal by small amounts of TP. The amount of stored LH in androgenized females was not different from that of normal females and it was unchanged by any dose of TP tested. Results are consistent with the conclusion that the male hypothalamic-hypophyseal axis is at least as sensitive as the female axis to the negative feedback effects of TP. Androgenization increases the sensitivity to TP in both males and females.


2021 ◽  
pp. svn-2020-000834
Author(s):  
Koteswara Rao Nalamolu ◽  
Bharath Chelluboina ◽  
Casimir A Fornal ◽  
Siva Reddy Challa ◽  
David M Pinson ◽  
...  

Background and purposeThe therapeutic potential of different stem cells for ischaemic stroke treatment is intriguing and somewhat controversial. Recent results from our laboratory have demonstrated the potential benefits of human umbilical cord blood-derived mesenchymal stem cells (MSC) in a rodent stroke model. We hypothesised that MSC treatment would effectively promote the recovery of sensory and motor function in both males and females, despite any apparent sex differences in post stroke brain injury.MethodsTransient focal cerebral ischaemia was induced in adult Sprague-Dawley rats by occlusion of the middle cerebral artery. Following the procedure, male and female rats of the untreated group were euthanised 1 day after reperfusion and their brains were used to estimate the resulting infarct volume and tissue swelling. Additional groups of stroke-induced male and female rats were treated with MSC or vehicle and were subsequently subjected to a battery of standard neurological/neurobehavioral tests (Modified Neurological Severity Score assessment, adhesive tape removal, beam walk and rotarod). The tests were administered at regular intervals (at days 1, 3, 5, 7 and 14) after reperfusion to determine the time course of neurological and functional recovery after stroke.ResultsThe infarct volume and extent of swelling of the ischaemic brain were similar in males and females. Despite similar pathological stroke lesions, the clinical manifestations of stroke were more pronounced in males than females, as indicated by the neurological scores and other tests. MSC treatment significantly improved the recovery of sensory and motor function in both sexes, and it demonstrated efficacy in both moderate stroke (females) and severe stroke (males).ConclusionsDespite sex differences in the severity of post stroke outcomes, MSC treatment promoted the recovery of sensory and motor function in male and female rats, suggesting that it may be a promising treatment for stroke.


2021 ◽  
pp. 074823372110105
Author(s):  
Roberta Tassinari ◽  
Andrea Martinelli ◽  
Mauro Valeri ◽  
Francesca Maranghi

Synthetic amorphous silica (SAS) nanomaterial – consisting of aggregates and agglomerates of primary silicon dioxide (SiO2) particles in the nanorange (<100 nm) – is commonly used as excipient in pharmaceuticals, in cosmetics and as food additive (E551). The available data suggest that SAS nanoparticles (NP) after intravenous (IV) exposure persist in liver and spleen; however, insufficient data exist to verify whether SAS may also induce adverse effects. The aim of the present study was to verify the potential long-term effects of SAS NP (NM-203) on spleen and liver as target organs following short-term exposure. Adult male and female Sprague-Dawley rats were treated by IV injection in the tail vein with a single (1-day) dose (SD) and repeated (5-day) doses (RD) of 20 mg/kg bw per day of SAS dispersed in sterile saline solution as vehicle. Histopathological examinations of target organs were performed after 90 days. Tissue biodistribution and full characterization of NM-203, primary particle size 13–45 nm, was performed within the framework of the Nanogenotox project. No mortality or general toxicity occurred; histopathological analysis showed splenomegaly in the RD group accompanied by inflammatory granulomas in both sexes. Granulomas were also present in liver parenchyma in the RD (both sexes) and SD groups (male only). The histopathological results indicated that SAS NP have the potential to persist and induce sex-specific chronic inflammatory lesions in spleen and liver upon short-term treatment. Overall, the data showed that the widespread use of silica in drugs might elicit chronic reactions in spleen and liver prompting to the need of further investigations on the safety of SAS NP.


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