RESUMEN
PURPOSE: The recent observation that urinary calcium excretion (UCE) drops considerably with CKD and that this effect may occur beyond compensation for reduced intestinal calcium absorption suggests that CKD per se is a state of sustained positive calcium balance, a mechanism likely to contribute to vascular calcification and CVD in CKD. However, the determinants of UCE reduction in CKD are not well understood and there is a lack of clinical studies, particularly in the CKD population. Therefore, in this study, we aimed to evaluate variables associated with UCE in a CKD cohort. METHODS: Baseline data on 356 participants of the Progredir Study, Sao Paulo, Brazil, essentially composed of CKD G3a-G4, were analyzed according to UCE (24 h urine collection). RESULTS: Median 24 h UCE was 38 mg/day (IQR 21-68 mg/day) and 0.48 mg/kg/day (IQR 0.28-0.82 mg/kg/day). In univariate analysis, UCE was inversely related to age, phosphorus, 1-84 PTH, FGF-23 and sclerostin, and positively associated with eGFR, DBP, 1,25(OH)2-vitamin D, calcium, bicarbonate, total calorie intake and spironolactone use. After adjustments for age, sex and eGFR, only 1,25(OH)2-vitamin D, calcium, FGF-23, bicarbonate and total calorie intake remained associated with it, but not PTH nor sclerostin. Lastly, in a multivariable model, eGFR, serum 1,25(OH)2-vitamin D, calcium, and FGF-23 remained associated with UCE. Similar results were observed when calcium fractional excretion was used instead of UCE, with eGFR, 1-25-vitamin D and FGF-23 remaining as independent associations. CONCLUSION: Our results showed that CKD is associated with very low levels of UCE and that 1,25(OH)2-vitamin D, serum calcium and FGF-23 were independently associated with UCE in this population, raising the question whether these factors are modulators of the tubular handling of calcium in CKD.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/fisiología , Calcitriol/fisiología , Factores de Crecimiento de Fibroblastos/fisiología , Hipercalciuria/etiología , Hormona Paratiroidea/fisiología , Insuficiencia Renal Crónica/complicaciones , Anciano , Estudios Transversales , Femenino , Factor-23 de Crecimiento de Fibroblastos , Humanos , MasculinoRESUMEN
A osteoporose é uma característica extra-articular bem estabelecida da artrite reumatoide (AR). A inflamação sistêmica parece ser essencial para causar uma alteração em múltiplos sistemas homeostáticos implicados na saúde óssea, como as vias RANK/RANKL/osteoprotegerina e Wnt/β catenina; vários outros fatores causais têm sido implicados, como o uso crônico de corticosteroides. Como a vitamina D exerce funções imunorreguladoras importantes, tem-se afirmado que o desarranjo do sistema vitamina D/hormônio paratireóideo (HPT), um determinante bem conhecido da saúde óssea, pode desempenhar um papel patogênico na autoimunidade; estudos com animais e dados clínicos apoiam essa hipótese. Além disso, os pacientes com AR parecem ser relativamente refratários à supressão de HPT induzida pela vitamina D. Portanto, a ligação entre a AR e a osteoporose pode ser em parte causada por alterações no sistema vitamina D/HPT. Uma melhor compreensão da fisiopatologia desse sistema pode ser crucial para prevenir e curar a osteoporose em pacientes com doenças inflamatórias/autoimunes. A maior evidência da correlação clínica de cooperação e interdependência entre a vitamina D e o HPT é que a correção da deficiência de vitamina D, pelo menos nas doenças autoimunes, deve ser orientada para a supressão do HPT.
Osteoporosis is a well-established extra-articular feature of rheumatoid arthritis (RA). Systemic inflammation seems to play a crucial role in causing an alteration of multiple homeostatic systems implied in bone health, such as the RANK/RANKL/Osteoprotegerin and Wnt/β catenin pathways; several other causal factors have been called into question, including the chronic use of corticosteroids. Since vitamin D exerts important immune-regulatory roles, it has been claimed that derangement of the vitamin D/parathyroid hormone (PTH) system, a well-known determinant of bone health, may play a pathogenic role in autoimmunity; animal models and clinical data support this hypothesis. Furthermore, RA patients seem to be relatively refractory to vitamin D-induced PTH suppression. Therefore, the link between RA and osteoporosis might in part be due to alterations in the vitamin D/PTH system. A better understanding of the pathophysiology of this system may be crucial to prevent and cure osteoporosis in patients with inflammatory/autoimmune diseases. A major clinical correlate of the strict cooperation and interdependence between vitamin D and PTH is that correction of the vitamin D deficiency, at least in autoimmune diseases, should be targeted to PTH suppression.
Asunto(s)
Humanos , Artritis Reumatoide/complicaciones , Osteoporosis/etiología , Hormona Paratiroidea/fisiología , Deficiencia de Vitamina D/complicaciones , Vitamina D/fisiología , Vitaminas/fisiologíaRESUMEN
Parathyroid hormone (PTH) is essential for the maintenance of calcium homeostasis through, in part, its actions to regulate bone remodeling. While PTH stimulates both bone formation and bone resorption, the duration and periodicity of exposure to PTH governs the net effect on bone mass, that is whether it is catabolic or anabolic. PTH receptor signaling in osteoblasts and osteocytes can increase the RANKL/OPG ratio, increasing both osteoclast recruitment and osteoclast activity, and thereby stimulating bone resorption. In contrast, PTH-induced bone formation is explained, at least in part, by its ability to downregulate SOST/sclerostin expression in osteocytes, permitting the anabolic Wnt signaling pathway to proceed. The two modes of administration of PTH, that is, continuous vs. intermittent, can regulate, in bone cells, different sets of genes; alternatively, the same sets of genes exposed to PTH in sustained vs. transient way, will favor bone resorption or bone formation, respectively. This article reviews the effects of PTH on bone cells that lead to these dual catabolic and anabolic actions on the skeleton.
Asunto(s)
Huesos/fisiología , Calcio/metabolismo , Hormona Paratiroidea/fisiología , Animales , Remodelación Ósea/fisiología , Resorción Ósea/metabolismo , Homeostasis , Humanos , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteocitos/metabolismoRESUMEN
Osteoporosis is a well-established extra-articular feature of Rheumatoid Arthritis (RA). Systemic inflammation seems to play a crucial role in causing an alteration of multiple homeostatic systems implied in bone health, such as the RANK/RANKL/Osteoprotegerin and Wnt/ß catenin pathways; several other causal factors have been called into question, including the chronic use of corticosteroids. Since vitamin D exerts important immune-regulatory roles, it has been claimed that derangement of the vitamin D/parathyroid hormone (PTH) system, a well-known determinant of bone health, may play a pathogenic role in autoimmunity; animal models and clinical data support this hypothesis. Furthermore, RA patients seem to be relatively refractory to vitamin D-induced PTH suppression. Therefore, the link between RA and osteoporosis might in part be due to alterations in the vitamin D/PTH system. A better understanding of the pathophysiology of this system may be crucial to prevent and cure osteoporosis in patients with inflammatory/autoimmune diseases. A major clinical correlate of the strict cooperation and interdependence between vitamin D and PTH is that correction of the vitamin D deficiency, at least in autoimmune diseases, should be targeted to PTH suppression.
Asunto(s)
Artritis Reumatoide/complicaciones , Osteoporosis/etiología , Hormona Paratiroidea/fisiología , Deficiencia de Vitamina D/complicaciones , Vitamina D/fisiología , Vitaminas/fisiología , HumanosRESUMEN
Recent years have witnessed a substantial increase in the number of seric determinations of vitamin D, in a worldwide basis. At Hospital das Clínicas of Faculdade de Medicina of Universidade de São Paulo that increase reached 700% over the last four years. Nevertheless there are many controversies on the literature about the role of vitamin D in conditions unrelated to the musculoskeletal system. In this study the metabolism, sources and actions of vitamin D on the body are reviewed. Observational studies, clinical trials, systematic reviews and metanalysis which focused on the relationship between the vitamin and conditions such as cancer, cardiovascular disease, diabetes and falls were searched on the literature, analyzed and discussed. Results are presented as quiz and answer, tables and a figure. The role of vitamin D on the above-mentioned conditions is discussed, and the controversial issues stressed.
Asunto(s)
Hormona Paratiroidea/fisiología , Deficiencia de Vitamina D/complicaciones , Vitamina D/fisiología , Accidentes por Caídas/prevención & control , Enfermedades Cardiovasculares/etiología , Colecalciferol/metabolismo , Ensayos Clínicos como Asunto , Diabetes Mellitus Tipo 2/etiología , Epidermis/metabolismo , Epidermis/efectos de la radiación , Estudios de Evaluación como Asunto , Humanos , Metaanálisis como Asunto , Neoplasias/etiología , Luz Solar , Vitamina D/sangreRESUMEN
O número de dosagens do nível sérico de vitamina D tem apresentado crescimento muito expressivo nos últimos anos em todo o mundo. No Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo houve aumento de cerca de 700% em quatro anos nas solicitações desse hormônio. No entanto, há controvérsias na literatura sobre a real utilidade de sua dosagem e/ou suplementação, exceto em situações diretamente relacionadas ao metabolismo ósseo. No presente trabalho são revistos o metabolismo, as fontes e as ações da vitamina D no organismo. Estudos observacionais, ensaios clínicos, revisões sistemáticas e metanálises, cujo foco é a relação entre vitamina D e doenças ou condições clínicas, como câncer, doenças cardiovasculares, diabetes e quedas, foram pesquisados na literatura, analisados e discutidos. Os resultados estão apresentados em forma de perguntas e respostas, tabelas e figura. Discute-se o papel da vitamina D em todas essas situações, e salientam-se os pontos controvertidos.
Recent years have witnessed a substantial increase in the number of seric determinations of vitamin D, in aworldwide basis. At Hospital das Clínicas of Faculdade de Medicina of Universidade de São Paulo that increase reached 700% over the last four years. Nevertheless there are many controversies on the literature about the role of vitamin D in conditions unrelated to themusculoskeletal system. In this study the metabolism, sources and actions of vitamin D on the body are reviewed. Observational studies, clinical trials, systematic reviews and metanalysis which focused on the relationship between the vitamin and conditions such as cancer, cardiovascular disease, diabetes and falls were searched on the literature, analyzed and discussed. Results are presented as quiz and answer, tables and a figure. The role of vitamin D on the above-mentioned conditions is discussed, and the controversial issues stressed.
Asunto(s)
Humanos , Hormona Paratiroidea/fisiología , Deficiencia de Vitamina D/complicaciones , Vitamina D/fisiología , Accidentes por Caídas/prevención & control , Enfermedades Cardiovasculares/etiología , Colecalciferol/metabolismo , Ensayos Clínicos como Asunto , /etiología , Epidermis/metabolismo , Epidermis/efectos de la radiación , Estudios de Evaluación como Asunto , Metaanálisis como Asunto , Neoplasias/etiología , Luz Solar , Vitamina D/sangreRESUMEN
Several clinical cases have shown the association of primary hyperparathyroidism and immune conditions related to B-cell hyperactivity. In some of these cases the treatment of hyperparathyroidism led to the resolution of the autoimmune phenomena. Thus, this paper hypothesizes that high levels of parathyroid hormone (PTH) may modify B lymphocytes function and induce the development of autoimmunity mediated by B-cell hyperactivity.
Asunto(s)
Linfocitos B/inmunología , Hiperparatiroidismo Primario/inmunología , Humanos , Modelos Teóricos , Hormona Paratiroidea/fisiologíaRESUMEN
La hipocalcemia es una complicación metabólica común en la tiroidectomía total y en el bypass gástrico. El mecanismo que la provoca es diferente en ambas entidades clínicas. La incidencia de esta complicación es variable, la presentación clínica es inespecífica y el manejo farmacológico no está estandarizado. Se presenta el caso clínico de una paciente de 40 años, a la cual se le realizaron ambas cirugías con el desarrollo de hipocalcemia sintomática post-operatoria.
Hypocalcemia is a common metabolic complications in total thyroidectomy and gastric bypass. The mechanism that causes it is different in both clinical entities. The incidence of this complication is variable, the clinical presentation is nonspecific and pharmacological management is not standardized. A case report of a patient of 40 years which were performed both surgeries with the development of postoperative symptomatic hypocalcemia.
Asunto(s)
Humanos , Adulto , Femenino , Derivación Gástrica/efectos adversos , Hipocalcemia/etiología , Tiroidectomía/efectos adversos , Hipocalcemia/fisiopatología , Hormona Paratiroidea/fisiología , Factores de Riesgo , Vitamina D/fisiologíaRESUMEN
Parathyroid hormone (PTH) functions as a major mediator of bone remodeling and as an essential regulator of calcium homeostasis. In this study, we investigated the role of PTH in the regulation of the cell cycle in human colon adenocarcinoma Caco-2 cells. Flow cytometry analysis revealed that PTH (10(-8)M, 12-24h) treatment increases the number of cells in the G0/G1 phase and diminishes the number in both phases S and G2/M. In addition, analysis by Western blot showed that the hormone increases the expression of the inhibitory protein p27Kip1 and diminishes the expression of cyclin D1, cyclin D3 and CDK6. However, the amounts of CDK4, p21Cip1, p15INK4B and p16INK4A were not different in the absence or presence of PTH. Inhibitors of PKC (Ro-318220, bisindolylmaleimide and chelerythine), but not JNK (SP600125) and PP2A (okadaic acid and calyculin A), reversed PTH response in Caco-2 cells. Taken together, our results suggest that PTH induces G0/G1 phase arrest of Caco-2 intestinal cells and changes the expression of proteins involved in cell cycle regulation via the PKC signaling pathway.
Asunto(s)
Adenocarcinoma/patología , Ciclo Celular/efectos de los fármacos , Neoplasias del Colon/patología , Hormona Paratiroidea/farmacología , Adenocarcinoma/metabolismo , Antracenos/farmacología , Antineoplásicos/farmacología , Benzofenantridinas/farmacología , Células CACO-2 , Ciclo Celular/fisiología , Neoplasias del Colon/metabolismo , Quinasas Ciclina-Dependientes/metabolismo , Evaluación Preclínica de Medicamentos , Fase G1/efectos de los fármacos , Fase G1/fisiología , Humanos , Indoles/farmacología , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/fisiología , Hormona Paratiroidea/fisiología , Proteína Quinasa C/antagonistas & inhibidores , Proteína Quinasa C/metabolismo , Proteína Quinasa C/fisiología , Inhibidores de Proteínas Quinasas/farmacología , Transducción de Señal/efectos de los fármacosRESUMEN
AIM: Coronary artery calcification (CAC) has been associated with higher mortality in chronic renal disease. The purpose of this study was to assess coronary artery calcium score (CaCs) in haemodialysis patients and to correlate calcium scores with clinical parameters and mortality. METHODS: A cross-sectional study was conducted in 59 haemodialysis patients. CaCs was assessed by multidetector-row computed tomography and stratified as: CaCs of less than 10 Agatston units (U), no calcification; CaCs of 10-400 U, mild-to-moderate; and CaCs of more than 400 U, severe calcification. The effects of age, haemodialysis duration and biochemical and inflammatory markers on CaCs logarithm were evaluated by multiple linear regression analysis. Cox regression analysis was used to measure the impact of CaCs of more than 400 on 2-year mortality. RESULTS: Coronary calcifications were detected in 64.5% of patients, and the median of CaCs was 31.7 U (0-589.7) with a range of 0-5790.0 U. Twenty-one (35.5%) patients had mild-to-moderate and 17 (29%) severe CaCs. Patients with severe CaCs were older and showed a higher prevalence of ischaemic heart disease and a higher body mass index (P=0.04). A trend towards higher C-reactive protein levels was found in patients with severe CaCs. Advanced age was the only variable that influenced CaCs logarithm independently. The effect of severe CaCs on 2-year mortality did not persist after adjustment for other covariates. CONCLUSION: Coronary calcification was highly prevalent in these uraemic patients on chronic haemodialysis. A correlation was evidenced between CaCs and advanced age, but severity of the CAC score did not have an impact on 2-year mortality of this cohort.
Asunto(s)
Calcinosis/mortalidad , Enfermedad de la Arteria Coronaria/mortalidad , Diálisis Renal/mortalidad , Adulto , Anciano , Proteína C-Reactiva/análisis , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/fisiología , Tomografía Computarizada por Rayos XRESUMEN
Parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25-(OH)zD] participate in systemic regulation of calcium homeostasis through endocrine effects mediated via the specific receptors PTHR1 and VDR, expressed in bone, kidney, intestine and parathyroid glands. In bone, both hormones PTH and 1,25-(OH)2D promote calcium release into the circulation; however, they also have anabolic effects in this tissue. In kidney, PTH controls 1,25-(OH)2D synthesis, and together both hormones stimulate calcium reabsorption. The most important calciotropic action of 1,25-(OH)2D is stimulation of intestinal calcium absorption. In the parathyroid glands, 1,25-(OH)2D regulates PTH synthesis through a negative feedback mechanism, while modulating the gland growth. Finally, a general overview of the maternal adaptations regarding calcium homeostasis during pregnancy and lactation is presented.
Asunto(s)
Calcio/metabolismo , Hormona Paratiroidea/fisiología , Vitamina D/análogos & derivados , Animales , Huesos/metabolismo , Calcio de la Dieta/farmacocinética , Retroalimentación Fisiológica , Femenino , Homeostasis , Humanos , Absorción Intestinal/fisiología , Intestino Delgado/metabolismo , Túbulos Renales Distales/metabolismo , Lactancia/fisiología , Mamíferos/metabolismo , Ratones , Glándulas Paratiroides/crecimiento & desarrollo , Glándulas Paratiroides/metabolismo , Embarazo , Vitamina D/fisiologíaRESUMEN
Hyperphosphatemia is a driving force in the pathogenesis of vascular calcification (VC) and secondary hyperparathyroidism associated with renal failure. To test for the possible contribution of parathyroid hormone (PTH) to cardiovascular calcification, we removed the parathyroid glands from rats but infused synthetic hormone at a supraphysiologic rate. All rats were pair-fed low, normal, or high phosphorus diets and subjected to a sham or 5/6 nephrectomy (remnant kidney). Control rats were given a normal diet and underwent both sham parathyroidectomy and 5/6 nephrectomy. Heart weight/body weight ratios and serum creatinine levels were higher in remnant kidney rats than in the sham-operated rats. Remnant kidney rats on the high phosphorus diet and PTH replacement developed hyperphosphatemia and hypocalcemia along with low bone trabecular volume. Remnant kidney rats on the low phosphorus diet or intact kidney rats on a normal phosphorus diet, each with hormone replacement, developed hypercalcemia. All rats on PTH replacement developed intense aortic medial calcification, and some animals presented coronary calcification. We suggest that high PTH levels induce high bone turnover and medial calcification resembling Mömckeberg's sclerosis independent of uremia. This model may be useful in defining mechanisms underlying VC.
Asunto(s)
Calcinosis/complicaciones , Enfermedades Cardiovasculares/complicaciones , Modelos Animales de Enfermedad , Hormona Paratiroidea/fisiología , Ratas , Insuficiencia Renal/etiología , Animales , Aorta/patología , Peso Corporal/efectos de los fármacos , Remodelación Ósea , Calcinosis/metabolismo , Calcinosis/patología , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/patología , Vasos Coronarios/patología , Ingestión de Alimentos/efectos de los fármacos , Hipercalcemia/etiología , Masculino , Hormona Paratiroidea/farmacología , Pletismografía , Ratas WistarRESUMEN
The principal function of the parathyroid hormone (PTH) is maintenance of calcium plasmatic levels, withdrawing the calcium from bone tissue, reabsorbing it from the glomerular filtrate, and indirectly increasing its intestinal absorption by stimulating active vitamin D (calcitriol) production. Additionally, the PTH prompts an increase in urinary excretion of phosphorus and bicarbonate, seeking a larger quantity of free calcium available in circulation. Two mechanisms may alter its function, limiting its control on calcium: insufficient PTH production by the parathyroids (hypoparathyroidism), or a resistance against its action in target tissues (pseudohypoparathyroidism). In both cases, there are significantly reduced levels of plasmatic calcium associated with hyperphosphatemia. Clinical cases are characterized by nervous hyperexcitability, with paresthesia, cramps, tetany, hyperreflexia, convulsions, and tetanic crisis. Abnormalities such as cataracts and basal ganglia calcification are also typical of these diseases. Treatment consists of oral calcium supplementation associated with increased doses of vitamin D derivatives.
Asunto(s)
Calcio/sangre , Hipoparatiroidismo/diagnóstico , Hormona Paratiroidea/fisiología , Seudohipoparatiroidismo/diagnóstico , Calcitriol/sangre , Calcio de la Dieta/administración & dosificación , Humanos , Hipocalcemia/sangre , Hipocalcemia/diagnóstico , Hipoparatiroidismo/sangre , Hipoparatiroidismo/tratamiento farmacológico , Hormona Paratiroidea/sangre , Fósforo/sangre , Seudohipoparatiroidismo/sangre , Seudohipoparatiroidismo/tratamiento farmacológico , Vitamina D/sangre , Vitamina D/uso terapéuticoRESUMEN
BACKGROUND: Adynamic bone disease is a type of renal osteodystrophy characterized by low bone turnover and paucity of bone cells. It was proposed that a new type of this disease featuring high osteoclastic resorption without parathyroid hormone stimulus and designated adynamic bone disease variant occurs in hemodialysis patients. The present study is designed to evaluate the frequency and characteristics of both diseases in a large series of bone biopsy specimens. METHODS: We reviewed 1,160 bone biopsy specimens from hemodialysis patients. Specimens in which adynamic bone disease was diagnosed were selected and categorized as classic or variant based on osteoclastic surface. RESULTS: In 218 bone biopsy specimens (18.8%), adynamic bone disease was identified, whereas the variant form was identified in 35 specimens (38.8%). Biopsy specimens categorized as the variant form were from patients who were younger and had greater phosphorus and parathyroid hormone levels. Histologically, the variant form presented greater osteoid volume, fibrosis volume, osteoid surface, osteoblast surface, and eroded surface. Similarly, values for all dynamic parameters were greater in the variant group. Osteoclastic surface correlated with phosphorus level, parathyroid hormone level, and osteoblast surface. Age and osteoblast surface were identified as independent determinants of the variant form. CONCLUSION: Adynamic bone disease variant seems to occur in younger hemodialysis patients with greater levels of parathyroid hormone, which acts on cell-covered bone surfaces. It probably is a transitional phase from low- to high-turnover status, rather than a true entity within the spectrum of renal osteodystrophy.
Asunto(s)
Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/etiología , Diálisis Renal/efectos adversos , Adulto , Edad de Inicio , Biopsia , Huesos/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Hormona Paratiroidea/fisiología , Estudios RetrospectivosRESUMEN
The concept of the role(s) of parathyroid hormone (PTH), has expanded from that on acting on the classical target tissues, bone and kidney, to the intestine where its actions are of regulatory and developmental importance: regulation of intracellular calcium through modulation of second messengers and, activation of mitogenic cascades leading to cell proliferation. Several causes have been postulated to modify the hormone response in intestinal cells with ageing, among them, alterations of PTH receptor (PTHR1) binding sites, reduced expression of G proteins and hormone signal transduction changes. The current review summarizes the actual knowledge regarding the molecular and biochemical basis of age-impaired PTH receptor-mediated signaling in intestinal cells. A fundamental understanding of why PTH functions are impaired with age will enhance our understanding of its importance in intestinal cell physiology.
Asunto(s)
Envejecimiento/fisiología , Intestinos/fisiología , Hormona Paratiroidea/fisiología , Receptor de Hormona Paratiroídea Tipo 1/metabolismo , Animales , Humanos , Intestinos/citología , Transducción de SeñalAsunto(s)
Humanos , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Enfermedades Óseas Metabólicas/fisiopatología , Hormona Paratiroidea/fisiología , Hormona Paratiroidea/uso terapéutico , Difosfonatos/uso terapéutico , Calcitonina/uso terapéutico , Moduladores de los Receptores de Estrógeno/uso terapéutico , Hormona del Crecimiento/uso terapéuticoRESUMEN
In mammals, neonatal positive calcium balance is required for adequate growth. Parathyroid hormone (PTH) plays a central role in this process mainly through its action on the distal nephron. We studied the effect of PTH on cytosolic calcium in distal segments from neonatal rat kidney. PTH elicited a concentration-dependent increase in cytosolic calcium in neonatal distal nephron (EC(50)=0.5 nM) but not in proximal tubules. At similar PTH concentrations the response was higher in the neonatal than in the adult tubules. The response was associated with protein kinase C (PKC), since phorbol myristate acetate (100 nM) increased [Ca(2+)]i, and staurosporin, an inhibitor of PKC, decreased (10 nM) or suppressed (100 nM) the PTH effect. cAMP analogues did not change [Ca(2+)]i. The response was diminished in low external calcium (0.1 mM) and absent at zero calcium, indicating dependency on external calcium. Resting calcium decreased from 80+/-10.8 to 28.6+/-2.6 nM at zero [Ca(2+)]e. PTH and nifedipine increased cytosolic calcium in an additive fashion. We show for the first time that PTH increased cytosolic calcium in the distal nephron of neonatal kidney, in a concentration-dependent pattern and in association with PKC activation. Higher sensitivity of the neonatal tubule might facilitate absorption of this cation during the neonatal period, when growth requires a positive balance of calcium.