Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sterility of male and female homozygous ob/ob mice is a recognized feature of the ob mutation (1). Whereas ob/ob males can occasionally reproduce if maintained on a restricted diet, ob/ob females are always sterile (2). Thinning of the ob/ob females to normal weight by diet-restriction failed to correct their sterility. Early sexual development is normal in ob/ob females; however, ovulation never follows and the mice remain prepuberal indefinitely with no occurrence of oestrus cycles. Reproductive hormones are reduced in ob/ob females (3) demonstrating a functional defect from the hypothalamic-pituitary axis (4-6). The ovaries of ob/ob females are capable of producing viable eggs when transplanted into lean female recipients (7). Reconstitution of reproductive functions in the ob/ob female necessitates delivery of hypothalamic extracts to the third ventricle (8) and administration of pituitary extract (9), gonadotropic hormones (10), progesterone (11) and relaxin (12). These previous findings demonstrate that the sterility of ob/ob females is caused by an insufficiency of hormones at the hypothalamic-pituitary level rather than physical hindrance of copulatory activity, pregnancy and parturition caused by excess adipose tissue. We show here that repeated administration of only the recombinant human ob protein, leptin, into homozygous female ob/ob mice can correct their sterility, thus resulting in ovulation, pregnancy and parturition.
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PMID:Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. 858 26

Numerous studies have revealed an association between nutritional status, adiposity, and reproductive maturity. The role of leptin, a hormone secreted from adipose tissue, in the onset of reproductive function was investigated. Normal prepubertal female mice injected with leptin grew at a slower rate than controls as a result of the hormone's thinning effects, but they reproduced up to 9 days earlier than controls and showed earlier maturation of the reproductive tract. These results suggest that leptin acts as a signal triggering puberty, thus supporting the hypothesis that fat accumulation enhances maturation of the reproductive tract.
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PMID:Early onset of reproductive function in normal female mice treated with leptin. 897

Bone loss and long-term persistence of osteoporosis with increased fracture risk are common after liver transplantation. It is unknown whether transplantation-induced disruption of hepatic nerves, serving numerous regulatory metabolic and sensory functions, is herein involved. To test this possibility, we measured bone mineral density (BMD) by peripheral quantitative computed tomography (pQCT) and studied dynamic histomorphometry, radiocalcium kinetics, and biochemical parameters in 7 liver-transplanted and 7 sham-operated inbred rats. Although liver function was normal in TX rats, trabecular BMD of the first lumbar vertebra and total BMD of the femoral diaphysis were decreased by 13% and 6%, respectively, 9 months postsurgery. The breaking force of the femur was significantly lower by 21%. However, bone mass in the femoral and tibial metaphysis was preserved as evidenced by pQCT measurements and histomorphometry. Trabecular width and wall thickness were significantly decreased in vertebral cancellous bone, whereas indices of bone formation and resorption were normal or slightly reduced. Serum minerals, mineral balance, fractional and net absorption of Ca and Mg, serum calciotropic hormones, IGF-I, leptin, specific activity of 45Ca in bone, 45Ca excretion, and biochemical indices of bone formation and bone resorption remained unchanged. We conclude that liver transplantation-related denervation causes cancellous and cortical bone loss in well-innervated bone sites such as the lumbar spine and the long bone diaphysis. Cancellous bone loss in TX rats is due to an impairment of osteoblast team performance and subsequent trabecular thinning. The mechanism uncovered by our study may contribute to long-term bone loss after liver transplantation.
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PMID:Regional bone loss after orthotopic liver transplantation in inbred rats: the role of hepatic denervation. 1220 Jun 52

This study was designed to evaluate the impact of estrogen versus androgen action on orchidectomy (ORX)-induced bone loss and associated changes in body composition. During an experimental period of 4 months, aged (12-month-old) ORX rats were treated with 17beta-estradiol (E2; 0.75 microg/day) or different doses of the nonaromatizable androgen 5alpha-dihydrotestosterone (DHT; 45, 75, and 150 microg/day, respectively), via subcutaneous (sc) silastic implants. Low doses of DHT and E2 inhibited the ORX-induced rise of bone turnover markers (serum osteocalcin and urinary deoxypyridinoline [DPD]) to a similar extent. High-dose DHT prevented the ORX-induced decrease of trabecular bone density but had no significant effect on cortical thinning as assessed by peripheral quantitative computed tomography (pQCT). This bone-sparing action of DHT occurred at the expense of hypertrophy of the ventral prostate and seminal vesicles. On the other hand, E2 restored both trabecular bone density and cortical thickness in ORX rats and even prevented age-related bone loss. In contrast to DHT, E2 increased lean body mass and inhibited the ORX-associated increase of fat mass, as measured by DXA. Administration of E2 was associated with increased serum concentrations of insulin-like growth factor (IGF) I and decreased circulating levels of leptin. We conclude that, in the aged ORX rat model, E2 is more effective in preventing ORX-induced bone loss than DHT. Additionally, E2 has anabolic effects on muscle tissue and prevents the ORX-related increase of fat mass. Overall, these data suggest that androgen action on bone and body composition is dependent on stimulation of both androgen receptors (ARs) and estrogen receptors (ERs).
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PMID:Evidence from the aged orchidectomized male rat model that 17beta-estradiol is a more effective bone-sparing and anabolic agent than 5alpha-dihydrotestosterone. 1241 16

Leptin is a hormone secreted by adipocytes that can regulate bone mass through a central, neuroendocrine signaling pathway. We tested the hypothesis that the response of bone tissue to altered leptin signaling is not uniform throughout the skeleton, but may vary between different skeletal regions and between cortical and trabecular moieties. We investigated the effects of leptin deficiency on muscle mass and bone architecture in obese, leptin-deficient (ob/ob) mice, and in lean controls. Results indicate that the obese mice weigh approximately twice as much as the lean mice, but the quadriceps muscles of the ob/ob mice are 40% smaller than those of controls. Leptin-deficient mice have significantly shorter femora, lower femoral bone mineral content (BMC), bone mineral density (BMD), cortical thickness, and trabecular bone volume compared to lean mice. Marrow tissue from the femora of ob/ob mice also shows a marked increase in adipocyte number compared to that of normal mice. In contrast to the pattern observed in the femur, ob/ob mice have significantly increased vertebral length, lumbar BMC, lumbar BMD, and trabecular bone volume compared to lean controls. Few adipocytes are observed in bone marrow from lumbar vertebrae of ob/ob mice, despite being numerous in marrow of the femur. However, like the femur, significant cortical thinning is also observed in the spine. These results indicate that the effects of altered leptin signaling on bone differ significantly between axial and appendicular regions, and may be mediated in part by muscle mass. The muscle hypoplasia, increased marrow adipogenesis, and decreased bone mass observed in the hindlimbs of ob/ob mice are also observed with aging in humans, suggesting that the ob/ob mouse may be a new and useful animal model for studying the relationship between bone marrow adipogenesis and osteopenia.
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PMID:Leptin deficiency produces contrasting phenotypes in bones of the limb and spine. 1500 83

The transition from uni- to multicellular organisms required metabolic cooperativity through cell-cell interactions mediated by soluble growth factors. We have empirically demonstrated such an integrating mechanism by which the metabolic hormone leptin stimulates lung development, causing the thinning of the gas exchange surface and the obligate increase in lung surfactant synthesis. All of these processes have occurred both phylogenetically and developmentally during the course of vertebrate lung evolution from fish to man. Here we show the integrating effects of the environmentally sensitive, pleiotropic hormone leptin on the development of the Xenopus laevis tadpole lung. The process described in this study provides a mechanistically integrated link between the metabolic regulatory hormone leptin and its manifold downstream effects on a wide variety of physiologic structures and functions, including locomotion and respiration, the cornerstones of land vertebrate evolution. It provides physiologic selection pressure at multiple levels to progressively generate Gene Regulatory Networks both within and between organs, from cells to systems. This model provides a cipher for understanding the evolution of complex physiology.
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PMID:Leptin stimulates Xenopus lung development: evolution in a dish. 1924 52

Environmental stress affects various parts of mammals typically through the circulation of stress hormones. It has been identified as one of the possible reasons for male reproductive difficulties, but the complex mechanisms responsible for stress-induced reproductive suppression are poorly understood. Here, we examined the relationship between chronic environmental stress and hypothalamic kisspeptin, a recently discovered upstream regulator of the reproductive endocrine feedback system. We studied male mice under an unpredictable chronic stress procedure to replicate the situation of animals under chronic stress. Histological and immunohistochemical analyses were performed focusing on kisspeptin neurons in the arcuate hypothalamic nucleus (ARC) and DNA fragmented cells in seminiferous tubules. Although the ARC was not morphologically altered in either the stressed or non-stressed group, granular kisspeptin immunoreactivities decreased slightly in the stress group. In the testes of the stress group, several signs of testicular degeneration were observed, including increased numbers of ssDNA-positive cells per seminiferous tubule, thinning, vacuoled seminiferous epithelia and multinucleated giant cells. The decreases in kisspeptin in the stress group might be due to other hypothalamic peptides, such as corticotropin-releasing hormone and leptin, whose receptors are known to coexpress in the ARC. In addition, environmental stress directly and indirectly affects testicular function through stress hormones and gonadotropins. In summary, our findings enhance the understanding of stress-induced reproductive suppression possibly mediated by kisspeptin in the ARC.
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PMID:Unpredictable chronic stress-induced reproductive suppression associated with the decrease of kisspeptin immunoreactivity in male mice. 2487 49