scholarly journals Selective β2-Adrenoceptor Blockade Rescues Mandibular Growth Retardation in Adolescent Rats Exposed to Chronic Intermittent Hypoxia

2021 ◽  
Vol 12 ◽  
Author(s):  
Haixin Hong ◽  
Jun Hosomichi ◽  
Hideyuki Maeda ◽  
Yuji Ishida ◽  
Risa Usumi-Fujita ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Growth Retardation ◽  
Adrenergic Receptors ◽  
Intermittent Hypoxia ◽  
Skeletal Growth ◽  
Chronic Intermittent Hypoxia ◽  
Rankl Expression ◽  
Mandibular Growth ◽  
Condylar Head

Activation of the sympathoadrenal system is associated with sleep apnea-related symptoms and metabolic dysfunction induced by chronic intermittent hypoxia (IH). IH can induce hormonal imbalances and growth retardation of the craniofacial bones. However, the relationship between IH and β2-adrenergic receptor signaling in the context of skeletal growth regulation is unclear. This study aimed to investigate the role of β2-adrenergic receptors in IH-induced mandibular growth retardation and bone metabolic alterations. Male 7-week-old Sprague–Dawley rats were subjected to IH for 3 weeks. IH conditions were established using original customized hypoxic chambers; IH was induced at a rate of 20 cycles per hour (oxygen levels changed from 4 to 21% in one cycle) for 8 h per day during the 12 h “lights on” period. The rats received intraperitoneal administration of a β2-adrenergic antagonist (butoxamine) or saline. To exclude dietary effects on general growth, the normoxic rats with saline, normoxic rats with butoxamine, and IH rats with butoxamine were subjected to food restriction to match the body weight gains between IH and other three groups. Body weight, heart rate, blood pressure, and plasma concentrations of leptin, serotonin, and growth hormone were measured. Bone growth and metabolism were evaluated using radiography, microcomputed tomography, and immunohistochemical staining. Plasma leptin levels were significantly increased, whereas that of serotonin and growth hormone were significantly decreased following IH exposure. Leptin levels recovered following butoxamine administration. Butoxamine rescued IH-induced mandibular growth retardation, with alterations in bone mineral density at the condylar head of the mandible. Immunohistochemical analysis revealed significantly lower expression levels of receptor activator of nuclear factor-kappa B ligand (RANKL) in the condylar head of IH-exposed rats. Conversely, recovery of RANKL expression was observed in IH-exposed rats administered with butoxamine. Collectively, our findings suggest that the activation of β2-adrenergic receptors and leptin signaling during growth may be involved in IH-induced skeletal growth retardation of the mandible, which may be mediated by concomitant changes in RANKL expression at the growing condyle.

Lack of growth hormone-dependent somatomedins or growth retardation in hypophysectomized fetal lambs

1985 ◽  
Vol 104 (2) ◽  
pp. 193-199 ◽  
Author(s):  
M. J. Parkes ◽  
D. J. Hill
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Growth Retardation ◽  
No Reduction ◽  
Fetal Plasma ◽  
Consistent Change

ABSTRACT Fetal lambs were hypophysectomized and, after 8 days of recovery, given infusions of GH, prolactin, thyroxine and insulin with glucose. Hypophysectomy caused no consistent reduction in fetal plasma somatomedin-like activity. Fetal infusions of GH or prolactin caused no consistent change in plasma somatomedin-like activity. It was concluded that fetal somatomedin-like activity is not GH dependent. After hypophysectomy fetal lambs showed no reduction in body weight or length at term. J. Endocr. (1985) 104, 193–199

Mandibular Growth Retardation in Growing Rats Chronically Exposed to Hypobaria

1987 ◽  
Vol 66 (1) ◽  
pp. 65-66 ◽  
Author(s):  
C.E. Bozzini ◽  
R.M. Alippi ◽  
A.C. Barcelo
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Growth Retardation ◽  
Body Weight Gain ◽  
Caloric Intake ◽  
Tail Length ◽  
Experimental Period ◽  
Close Relation ◽  
Exposure Period ◽  
Mandibular Growth

Weanling male Wistar rats aged 21 days were divided into three groups: initial control, normobaric, and hypobaric (C, N, and H, respectively). C rats were killed three days after being weaned. H rats were placed into an altitude chamber and maintained at 456 mb (6100 m) for 14 days. N rats were maintained at sea-level conditions. Body weight, body and tail lengths, and food intake were recorded every day. Animals were killed at the end of the experimental period, and four linear dimensions of the dried mandible were measured. The amount of food eaten by the H rats during the entire exposure period was 54.6% of that consumed by N ones. Body weight gain in H rats was 32.7% of that seen in N rats. Body length was 49.0% and tail length was 56.6% of normal. All mandibular dimensions were significantly reduced in H rats when compared with N rats and were, in general, in close relation with the reduction observed in skeletal growth. Only one dimension was reduced out of proportion, which indicates some deformation of the mandible. The average daily caloric intake related to metabolic body weight (body weight0.75) of H rats was 60% of the N value. Efficiency of protein utilization for growth was not significantly different between both groups of rats. These results indicate that chronic exposure to hypobaria induces overall skeletal and mandibular growth retardation, which appears to be the result of a diminution in food intake because of decreased appetite.

scholarly journals Comparison of Sulfate Metabolism in Costal Cartilage of Normal and 'Little' Mice

1983 ◽  
Vol 36 (3) ◽  
pp. 263 ◽  
Author(s):  
NeiI M McKern
Keyword(s):  
Growth Hormone ◽  
Growth Rate ◽  
Body Weight ◽  
Costal Cartilage ◽  
Cartilage Degradation ◽  
Skeletal Growth ◽  
Sulfate Uptake ◽  
Sulfate Metabolism ◽  
C 50

C57BL/6J and mutant 'little' (lit/lit) mice c. 50 days of age were injected with doses of [35S]sulfate proportional to their body weight. Despite the diminished growth rate of lit/lit mice compared with normal mice at this age, uptake of radioactivity per unit mass of cartilage was similar for both mouse types, confirming previous data. Additional experiments with these mice established that the similarity of sulfate uptake could not be accounted for by differences in the location of bound sulfate or (for females) by differences in cartilage cellularity. Investigation of sulfate loss by costal cartilage in vivo indicated that cartilage degradation occurred at a greater rate in lit/lit mice than in normally growing mice. These latter data suggest that growth hormone, which is lacking in lit/lit mice, may in part regulate skeletal growth (at least for female mice) by inhibiting degradation of cartilage.

Intermittent hypoxia retards mandibular growth and alters RANKL expression in adolescent and juvenile rats

2020 ◽  
Author(s):  
Haixin Hong ◽  
Jun Hosomichi ◽  
Hideyuki Maeda ◽  
Kochakorn Lekvijittada ◽  
Shuji Oishi ◽  
...  
Keyword(s):  
Intermittent Hypoxia ◽  
Bone Growth ◽  
Receptor Activation ◽  
Growth Stages ◽  
Mineral Density ◽  
Juvenile Rats ◽  
Mandibular Growth ◽  
Obstructive Sleep ◽  
Condylar Head ◽  
Adolescent Rats

Summary Objectives Chronic intermittent hypoxia (IH), a common state experienced in obstructive sleep apnoea (OSA), retards mandibular growth in adolescent rats. The aim of this study was to elucidate the differential effects of IH on mandibular growth in different growth stages. Materials and methods Three-week-old (juvenile stage) and 7-week-old (adolescent stage) male Sprague–Dawley rats underwent IH for 3 weeks. Age-matched control rats were exposed to room air. Mandibular growth was evaluated by radiograph analysis, micro-computed tomography, real-time polymerase chain reaction and immunohistology. Tibial growth was evaluated as an index of systemic skeletal growth. Results IH had no significant impact on the general growth of either the juvenile or adolescent rats. However, it significantly decreased the total mandibular length and the posterior corpus length of the mandible in the adolescent rats and the anterior corpus length in the juvenile rats. IH also increased bone mineral density (BMD) of the condylar head in adolescent rats but did not affect the BMD of the tibia. Immunohistological analysis showed that the expression level of receptor activation of nuclear factor-κB ligand significantly decreased (in contrast to its messenger ribonucleicacid level) in the condylar head of adolescent rats with IH, while the number of osteoprotegerin-positive cells was comparable in the mandibles of adolescent IH rats and control rats. Limitations The animal model could not simulate the pathological conditions of OSA completely and there were differences in bone growth between humans and rodents. Conclusions These results suggest that the susceptibility of mandibular growth retardation to IH depends on the growth stage of the rats.

Effect of exogenous growth hormone on somatic growth, gonadal development, and hepatic CYP2C11 and CYP2C12 expression in prepubertal intact male rats

2001 ◽  
Vol 79 (4) ◽  
pp. 352-361
Author(s):  
Masahiko Kawai ◽  
Stelvio M Bandiera ◽  
Thomas KH Chang ◽  
Gail D Bellward
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Cytochrome P450 ◽  
Somatic Growth ◽  
Skeletal Growth ◽  
Male Rats ◽  
Intact Male ◽  
Hepatic Expression ◽  
Testicular Weight ◽  
Exogenous Growth

The influence of exogenous growth hormone (GH) on pubertal maturation, as assessed by growth, age of preputial separation, testicular development, and hepatic expression of sexually dimorphic cytochrome P450 (CYP) enzymes, was investigated. Treatment of 22-day old prepubertal intact male rats with twice daily subcutaneous (sc) injections of rat recombinant GH (0.12 µg/g body weight) for 12 or 21 days did not affect body weight, skeletal growth, or testicular weight. By comparison, GH suppressed hepatic CYP2C11 enzyme activity, protein, and mRNA levels but induced CYP2C12 expression. GH suppressed CYP2C11 expression by approximately 60% in prepubertal rats as compared with 30% in adult rats, whereas it increased CYP2C12 levels to 80% of the normal female levels but had no effect in adult male rats. Twice daily intravenous injections of GH suppressed CYP2C11 only. Increasing the sc dose of GH 30-fold produced little or no additional change in CYP2C11 or CYP2C12 expression, whereas it modestly increased body weight and skeletal growth and reduced testicular weight. Overall, the present study provides the first demonstration that prepubertal administration (22-33 days of age) of GH at a pharmacologically relevant dose (0.12 µg/g twice daily) suppressed hepatic expression of CYP2C11 in 34-day-old intact male rats, suggesting that in this age group the liver is intrinsically responsive to transcription factors involved in the regulation of GH-dependent, sex-specific CYP gene expression. A higher dose (3.6 µg/g) of GH administered during the prepubertal period was required to elicit a modest effect on somatic growth and gonadal development.Key words: cytochrome P450, CYP2C11, CYP2C12, growth hormone, preputial separation, pubertal development, testosterone.

scholarly journals Intermittent hypoxia in utero damages postnatal growth and cardiovascular function in rats

2018 ◽  
Vol 124 (4) ◽  
pp. 821-830 ◽  
Author(s):  
Ling Chen ◽  
Zahra Heidari Zadi ◽  
Jin Zhang ◽  
Steven M. Scharf ◽  
Eung-Kwon Pae
Keyword(s):  
Blood Pressure ◽  
Obstructive Sleep Apnea ◽  
Body Weight ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Cardiovascular Function ◽  
Left Ventricular ◽  
Chronic Intermittent Hypoxia ◽  
Tibial Length ◽  
Obstructive Sleep

Obstructive sleep apnea (OSA) is common in pregnancy and may compromise fetal and even postnatal development. We developed an animal model to determine if maternal OSA could have lasting effects in offspring. Pregnant Sprague-Dawley rats were exposed to reduced ambient O2 from 21 to 4–5%, approximately once per minute [chronic intermittent hypoxia (CIH)] for 8 h/day during gestation days 3–19. Similarly handled animals exposed to ambient air served as controls (HC). Offspring were studied for body growth and cardiovascular function for 8 postnatal weeks. Compared with HC, prenatal CIH led to growth restriction, indicated by smaller body weight and tibial length, and higher arterial blood pressure in both male and female offspring. Compared with same-sex HC, CIH males showed abdominal obesity (greater ratio of abdominal fat weight to body weight or tibial length), left ventricular (LV) hypertrophy (greater heart weight-to-tibial length ratio and LV posterior wall diastolic thickness), elevated LV contractility (increases in LV ejection fraction, end-systolic pressure-volume relations, and preload recruitable stroke work), elevated LV and arterial stiffness (increased end-diastolic pressure-volume relationship and arterial elasticity), and LV oxidative stress (greater lipid peroxide content). Compared with female CIH offspring, male CIH offspring had more profound changes in blood pressure (BP), cardiac function, myocardial lipid peroxidase (LPO) content, and abdominal adiposity. Rodent prenatal CIH exposure, mimicking human maternal OSA, exerts detrimental morphological and cardiovascular effects on developing offspring; the model may provide useful insights of OSA effects in humans. NEW & NOTEWORTHY Obstructive sleep apnea is common in human pregnancy. Following maternal exposure to chronic intermittent hypoxia, a hallmark of sleep apnea, both sexes of rat offspring showed growth retardation, with males being more vulnerable to hypertension and dysfunctional left ventricular changes. This model is useful to study detrimental effects of maternal obstructive sleep apnea on developing offspring in humans.

Intermittent hypoxia causes mandibular growth retardation and macroglossia in growing rats

2017 ◽  
Vol 151 (2) ◽  
pp. 363-371 ◽  
Author(s):  
Jun Hosomichi ◽  
Yo-ichiro Kuma ◽  
Shuji Oishi ◽  
Hisashi Nagai ◽  
Hideyuki Maeda ◽  
...  
Keyword(s):  
Growth Retardation ◽  
Intermittent Hypoxia ◽  
Mandibular Growth ◽  
Growing Rats

scholarly journals Mice Exposed to Chronic Intermittent Hypoxia Simulate Clinical Features of Deficiency of both Qi and Yin Syndrome in Traditional Chinese Medicine

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Chengzhi Chai ◽  
Junping Kou ◽  
Danni Zhu ◽  
Yongqing Yan ◽  
Boyang Yu
Keyword(s):  
Animal Model ◽  
Body Weight ◽  
Chinese Medicine ◽  
Food Intake ◽  
Traditional Chinese Medicine ◽  
Clinical Features ◽  
Intermittent Hypoxia ◽  
Bleeding Time ◽  
Chronic Intermittent Hypoxia ◽  
Locomotive Activity

Deficiency of both Qi and Yin Syndrome (DQYS) is one of the common syndromes in traditional Chinese medicine (TCM), mainly characterized by tiredness, emaciation, anorexia, fidget, palpitation and rapid pulse, and so forth. Currently, there is no available animal model which can reflect the clinical features of this syndrome. In the present paper, we observed the time-course changes of whole behavior, body weight, food intake, locomotive activity and electrocardiogram in mice exposed to chronic intermittent hypoxia for 6 weeks, and measured bleeding time at last according to the clinical features of DQYS and one key pathological factor. The results showed that the mice exposed to intermittent hypoxia for certain time presented lackluster hair, dull looking hair, resistance, attacking, body weight loss, food intake decline, locomotive activity decrease, heart rate quickening and T wave elevating, which were similar to the major clinical features of DQYS. Meanwhile, bleeding time shortening was also found, which was consistent with the clinical fact that DQYS often accompanied with blood stasis. The possible explanation was also outlined according to the available literature. Such findings suggested chronic intermittent hypoxia could induce similar symptoms and signs in mice accorded with the clinical features of DQYS, which provided a suitable animal model for evaluation of drugs for the treatment of this syndrome and further exploration of pathological process or correlation of the syndrome and related diseases.

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