Estrogen receptor-alpha and -beta are expressed throughout postnatal development in the rat and rabbit growth plate.

Estrogen regulates skeletal growth and promotes epiphyseal fusion. To explore the mechanisms underlying these effects we investigated the expression of estrogen receptor-alpha (ERalpha) and -beta (ERbeta) in rat and rabbit growth plates during postnatal development, using immunohistochemistry. Immunoreactivity for ERalpha and ERbeta was observed in resting zone and proliferative zone chondrocytes at all ages studied for both rat (7, 14, 28 and 70 days of age) and rabbit (1, 7, 28 and 120 days of age). In the rat distal humerus and the rabbit proximal tibia, expression of both receptors in the hypertrophic zone was minimal at early ages, increasing only at the last time point prior to epiphyseal fusion. Expression was rarely seen in the hypertrophic zone of the rat proximal tibia, a growth plate that does not fuse until late in life. Therefore, we conclude that ERalpha and ERbeta are both expressed in the mammalian growth plate. The temporal and anatomical pattern suggests that ER expression in the hypertrophic zone in particular may play a role in epiphyseal fusion.

Uso de sedación para la realización de biopsia de próstata guiada por ecografía transrectal y su impacto en la calidad de vida del paciente / Sedation for the accomplishment of transrectal echographic guided prostate biopsy and its impact on the patient's quality of life

La biopsia de próstata guiada por ecografía transrectal ha revolucionado la detección del cáncer de próstata, sin embargo, existen pocos ensayos a nivel nacional del impacto de este procedimiento en la calidad de vida de los pacientes, más aún, si consideramos que estudios recientes han sugerido incrementar el número de muestras para aumentar la sensibilidad de este examen. El objetivo de este trabajo fue determinar el impacto en la calidad de vida de los pacientes sometidos a biopsia de próstata guiada por ecografía transrectal en 6 y 12 muestras y demostrar la utilidad de la sedación durante el examen. Se randomizaron 60 pacientes, del Servicio de Urología del Hospital San José, en dos grupos: 30 pacientes con sedación (Midazolam 2,5 mg endovenoso) y 30 pacientes con placebo. Estos grupos se subdividieron en grupos de 6 y 12 muestras de tejido prostático. Se constató edad, antígeno prostático, tacto rectal, comorbilidad y complicaciones post biopsia. Todos los pacientes contestaron un cuestionario realizado post examen y un segundo cuestionario 4 semanas después. La calidad de vida fue evaluada utilizando 2 escalas (Short form 36 item health survey). La edad promedio de los pacientes fue de 70 años, con valores de antígeno prostático entre 4,6- 281 ng/dl. Al comparar los grupos sometidos a sedación (6 y 12 muestras) versus los grupos sin sedación sometidos a biopsia transrectal guiada por ecografía, se encuentran diferencias estadísticamente significativas (p<0,0005). Las complicaciones de la sedación en el procedimiento fueron 0 por ciento. Se discuten los resultados.

Effects of estrogen on growth plate senescence and epiphyseal fusion.

Estrogen is critical for epiphyseal fusion in both young men and women. In this study, we explored the cellular mechanisms by which estrogen causes this phenomenon. Juvenile ovariectomized female rabbits received either 70 microg/kg estradiol cypionate or vehicle i.m. once a week. Growth plates from the proximal tibia, distal tibia, and distal femur were analyzed after 2, 4, 6, or 8 weeks of treatment. In vehicle-treated animals, there was a gradual senescent decline in tibial growth rate, rate of chondrocyte proliferation, growth plate height, number of proliferative chondrocytes, number of hypertrophic chondrocytes, size of terminal hypertrophic chondrocytes, and column density. Estrogen treatment accelerated the senescent decline in all of these parameters. In senescent growth plates, epiphyseal fusion was observed to be an abrupt event in which all remaining chondrocytes were rapidly replaced by bone elements. Fusion occurred when the rate of chondrocyte proliferation approached zero. Estrogen caused this proliferative exhaustion and fusion to occur earlier. Our data suggest that (i) epiphyseal fusion is triggered when the proliferative potential of growth plate chondrocytes is exhausted; and (ii) estrogen does not induce growth plate ossification directly; instead, estrogen accelerates the programmed senescence of the growth plate, thus causing earlier proliferative exhaustion and consequently earlier fusion.

Leptin secretion in Cushing's syndrome: preservation of diurnal rhythm and absent response to corticotropin-releasing hormone.

The normal inverse relationship between leptin and cortisol is lost in chronic hypercortisolism. We studied this apparent dysregulation in patients with Cushing's syndrome to investigate 1) the effect of chronic hypercortisolemia on the circadian rhythm of leptin secretion, 2) the response of leptin after administration of CRH, and 3) the short term effect of curative surgery on leptin. The preoperative morning leptin concentration was 54.2 +/- 8.1 ng/mL, and the nighttime value was 68.6 +/- 9.8 ng/mL, reflecting a mean rise of 32.8 +/- 7.6%, similar to the nocturnal increase observed in normal subjects. By contrast, cortisol's diurnal variation (21.8 +/- 1.7 vs. 16.9 +/- 1.1 mg/dL) was blunted. In women, but not men, body mass index correlated with leptin (P = 0.001). Preoperative ACTH and cortisol (both P < 0.0001), but not leptin levels increased after CRH. Ten days after surgery, basal cortisol values were subnormal (1.1 +/- 0.6 mg/dL), but leptin levels remained unchanged and did not increase after CRH. Body mass index and insulin also remained unchanged. Insulin, but not age, urinary free cortisol, or plasma cortisol correlated with leptin (P < 0.05). In summary, patients with Cushing's syndrome have moderately elevated leptin levels that maintain an intact circadian rhythm but do not respond to acute or subacute alterations of cortisol.

Determinants of spatial polarity in the growth plate.

Growth of long bones occurs at the growth plate, a layer of cartilage that separates the epiphysis from the metaphysis. Growth plate exhibits spatial polarity. Proliferative chondrocytes undergo terminal differentiation when they approach the metaphyseal, but not the epiphyseal, border of the growth plate. The adjacent bone also exhibits spatial polarity. Metaphyseal, but not epiphyseal, blood vessels and bone cells invade the adjacent growth plate, remodeling it into bone. As a result, the metaphysis, but not the epiphysis, elongates over time. To determine whether cartilage polarity determines bone polarity and/or whether bone polarity determines cartilage polarity, rabbit distal ulnar growth plates were excised, inverted, and reimplanted in their original beds. Thus, cartilage polarity was inverted relative to bone polarity. Histological examination showed that the inverted cartilage polarity was maintained over time. In contrast, the polarity of the adjacent bone reversed after surgery, to match that of the cartilage. Blood vessel and bone cell invasion ceased in the metaphysis and arose in the epiphysis. Longitudinal bone growth (measured with weekly radiographs) occurred at the epiphyseal, not at the metaphyseal, surface of the growth plate. We conclude that the polarity of growth plate cartilage is determined by intrinsic factors. The cartilage polarity then determines the polarity of the adjacent bone and, consequently, the functional polarity of longitudinal bone growth.