RESUMEN
Serum levels of IGF-I were measured in Barbadian children, aged 9-15 years, half of whom had experienced protein-energy malnutrition limited to the first year of life. Despite current nutritional adequacy, menarche was delayed more than one year in the girls with a history of early malnutrition and their IGF-I levels failed to show the 60% postmenarchic increase seen in the controls. In addition, the IGF-I levels of boys and girls with prior malnutrition in infancy were not significantly correlated with current anthropometric measurements, whereas IGF-I values of control boys and girls were significantly correlated for almost every growth parameter. Infantile malnutrition may cause an alteration in hypothalamic function resulting both in delayed onset of hypothalamic pituitary functions needed for puberty, and in an impaired growth hormone-IGF-I response.
Asunto(s)
Ensayos Clínicos como Asunto/tendencias , Predicción , Apoyo a la Investigación como Asunto/tendencias , Investigación/tendencias , Ensayos Clínicos como Asunto/economía , Ensayos Clínicos como Asunto/normas , Humanos , Investigación/economía , Investigación/normas , Investigadores/educación , Investigadores/normas , Investigadores/estadística & datos numéricos , Apoyo a la Investigación como Asunto/economía , Apoyo a la Investigación como Asunto/normas , Estados UnidosRESUMEN
This investigation assessed the syndromal nature of menstrual cycle changes in women who experience significant cyclicity of mood by exploring the time course of different symptoms in relation to endocrinologically defined segments of the menstrual cycle. Participants were accepted into the protocol on the basis of a prospectively documented history of perimenstrual mood change. The protocol included completion of the Daily Life Experiences Questionnaire and blood sampling during three menstrual cycles. The syndromal nature of menstrual cycle changes was explored by determining the types of symptoms which fluctuated in relation to five endocrinologically defined segments of the menstrual cycle, and the time course of the symptom changes. The results further document the temporal association between the luteal phase and the onset of perimenstrual symptoms and suggest that the syndromal nature of menstrual cycle-related changes may differ for women who experience different intensities of cyclical mood.
Asunto(s)
Hormonas Esteroides Gonadales/sangre , Ciclo Menstrual , Síndrome Premenstrual/psicología , Adulto , Estradiol/sangre , Femenino , Humanos , Hormona Luteinizante/sangre , Síndrome Premenstrual/sangre , Progesterona/sangre , Pruebas PsicológicasRESUMEN
A major portion of the hCG immunoreactivity detectable in pregnancy urine is derived from a fragment of hCG beta. This lacks the COOH-terminal portion of hCG beta, but retains immunoreactivity with most antibodies raised against the beta-subunit of hCG. To improve clinical measurements of hCG and assess the importance of such fragments in human urine, we have isolated and determined the structure of this molecule. The hCG beta fragment was isolated from a partially purified commercial preparation of hCG (Organon) by gel filtration and immunoaffinity chromatography using monoclonal antibodies. It was found to consist of two polypeptide chains composed of residues beta-(6-40) disulfide-bridged to residues beta-(55-92). It also differs from the beta-subunit of hCG in its carbohydrate structure, lacking sialic acid and having a low but variable amount of galactose. A beta-fragment containing the same two NH2-terminal sequences was also isolated from a single pregnant woman's urine. The two major polypeptides comprising the beta-fragment contain a total of nine half-cystine residues, raising the possibility that a free thiol may exist or that a third undetected disulfide-bridged peptide is present in the intact fragment. However, tests for the presence of a free thiol have been negative. Another intrinsic characteristic of the beta-fragment is the formation of a variable amount of dimer in solutions of neutral pH. beta-fragment will not combine with intact alpha-subunit. Despite the absence of regions beta-(1-5), beta-(41-54), and beta-(93-145), the beta fragment is recognized by the SB-6 antibody and most monoclonal antibodies elicited to the beta-subunit, thus excluding half of the amino acids of the beta-subunit from the epitope(s) where these antibodies bind.
Asunto(s)
Gonadotropina Coriónica/orina , Fragmentos de Péptidos/orina , Embarazo/orina , Secuencia de Aminoácidos , Gonadotropina Coriónica/aislamiento & purificación , Gonadotropina Coriónica Humana de Subunidad beta , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Sustancias Macromoleculares , Datos de Secuencia Molecular , Peso Molecular , Fragmentos de Péptidos/aislamiento & purificaciónRESUMEN
Menstrual cycle changes associated with vigorous exercise can range widely. They may be only subtle abnormalities, ranging from delayed onset of spontaneous menses or anovulatory cycles to loss of spontaneous menses. They may be more serious, however. Significant adverse bone mineral changes, resulting in clinically significant osteoporosis and fractures, may occur concomitantly with exercise-induced menstrual dysfunction.
Asunto(s)
Amenorrea/etiología , Esfuerzo Físico , Amenorrea/fisiopatología , Composición Corporal , Huesos/fisiopatología , Femenino , Humanos , Menarquia , Ciclo Menstrual , Estado Nutricional , Paridad , Estrés Psicológico/complicacionesAsunto(s)
Síndrome del Ovario Poliquístico/terapia , Andrógenos/metabolismo , Bromocriptina/uso terapéutico , Dexametasona/uso terapéutico , Femenino , Genes Dominantes , Hirsutismo/etiología , Humanos , Sistema Hipotálamo-Hipofisario/fisiopatología , Infertilidad Femenina/etiología , Obesidad/etiología , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/genética , Síndrome del Ovario Poliquístico/fisiopatologíaAsunto(s)
Bromocriptina/uso terapéutico , Hormonas Esteroides Gonadales/metabolismo , Ciclo Menstrual/efectos de los fármacos , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Femenino , Gonadotropinas Hipofisarias/metabolismo , Humanos , Síndrome del Ovario Poliquístico/metabolismo , Síndrome del Ovario Poliquístico/fisiopatologíaRESUMEN
The subcellular metabolism of internalized hCG was examined by monitoring the distribution of bioactive and immunoreactive hCG in subcellular fractions of pseudopregnant rat ovaries. Homogenates of ovaries from rats injected with 1.0 microgram (12.8 IU; bioassay) hCG were fractionated on self-generating Percoll gradients into three hCG-containing compartments: soluble proteins (cytosolic fraction), a combined plasma membrane/prelysosomal vesicle fraction, and lysosomes. The hCG level in each fraction was measured by RIA and in vitro bioassay. When necessary, receptor-bound hCG was dissociated at low pH before assay. Levels of cytosolic hCG were highest 1-3 h after injection, attaining peak immunoreactive concentrations of 18 ng/ovarian pair. Cytosolic hormone was not primarily derived from nonspecific trapping of serum or interstitial fluid, because after 1.0 microgram [125I]iodobovine gamma-globulin was injected into rats, cytosolic globulin levels (nanograms per ovarian pair) were approximately 7-10 times lower than those of hCG. Cytosolic hCG retained significant bioactivity for at least 10 h after hCG stimulation. Peak immunoreactive hCG levels associated with the plasma membrane/prelysosomal fraction were 82 ng/ovarian pair between 3 and 6 h after hCG injection, and hormone associated with that fraction retained the highest bioactivity of the three fractions examined. Peak lysosomal hCG levels reached 55 ng/ovarian pair 10 and 14 h after hCG stimulation, but lysosomal hCG was not bioactive. These results suggest that the lysosomal compartment is a major pathway for hCG inactivation. A nonlysosomal pathway for hCG inactivation may exist, because the cytosolic compartment contained partially inactivated hormone that did not appear to be of lysosomal origin. Cytosolic hCG may reflect hormone delivered to the cell cytoplasm or to the extracellular fluid that is either modified within prelysosomal vesicles or is degraded subsequently by nonlysosomal proteases.
Asunto(s)
Gonadotropina Coriónica/metabolismo , Ovario/metabolismo , Seudoembarazo/metabolismo , Animales , Compartimento Celular , Membrana Celular/análisis , Citosol/análisis , Endocitosis , Femenino , Humanos , Lisosomas/análisis , Ratas , Distribución TisularRESUMEN
To determine if human luteinizing hormone (hLH) follows the same subcellular route in the pseudo-pregnant rat ovary as human chorionic gonadotropin (hCG), the distribution of immunoreactive and bioactive hLH within cytosol, lysosomes, and a combined plasma membrane/prelysosomal vesicle fraction was examined. Immunoreactive levels were determined using a specific radioimmunoassay and bioactive levels were determined in an in vitro Leydig cell bioassay. Low cytosolic hLH levels were apparent the first few hours after hLH administration and may reflect at least some contamination by serum and interstitial fluid. Plasma membrane/prelysosomal vesicles attained the highest hLH concentration 1 h after hLH injection, after which hLH levels declined rapidly until barely detectable levels were observed at 18 h. The hormone in this fraction was receptor bound and exhibited the highest bioactivity of the three fractions examined. Lysosomal hLH concentrations were highest at 12 after hLH injection and were maintained at high levels through 18 h. Substantial amounts of lysosomal hLH appeared to be receptor bound but this hormone was not bioactive. In situ degradation of the oligosaccharides may have occurred while lysosomal hLH was receptor bound. Lysosomal degradation is the major pathway for hLH inactivation as has been described for hCG. However, hLH may be degraded within lysosomes more quickly than hCG. The differential subcellular distribution of immunoreactive and bioactive hLH provides strong support for hLH internalization and degradation within ovarian luteal cells.
Asunto(s)
Hormona Luteinizante/metabolismo , Ovario/metabolismo , Fracciones Subcelulares/metabolismo , Animales , Bioensayo , Compartimento Celular , Membrana Celular/metabolismo , Centrifugación por Gradiente de Densidad , Citosol/metabolismo , Femenino , Lisosomas/metabolismo , Radioinmunoensayo , Ratas , Ratas EndogámicasRESUMEN
Of 50 consecutive women with partial seizures of temporal lobe origin (temporal lobe epilepsy [TLE]) evaluated for reproductive dysfunction, 28 had menstrual problems. Of those, 19 had reproductive endocrine disorders. Polycystic ovarian syndrome and hypogonadotropic hypogonadism occurred significantly more often in women with TLE than in the general female population. Polycystic ovarian syndrome was associated with predominantly left-sided lateralization of interictal epileptic discharges; hypogonadotropic hypogonadism was more commonly found with right-sided discharges. Hyposexuality occurred more often in women with predominantly right-sided interictal epileptic discharges and was associated with low serum luteinizing hormone levels. There are several possible interpretations: epileptic discharges in medial temporal limbic structures may disrupt hypothalamic regulation of pituitary gonadotropin secretion; anovulatory cycles of reproductive endocrine disorders may promote the development of epileptic discharges; and TLE and some associated reproductive endocrine disorders may represent the parallel effects of prenatal factors common to the development of the brain and the reproductive system.
Asunto(s)
Enfermedades del Sistema Endocrino/complicaciones , Epilepsia del Lóbulo Temporal/complicaciones , Adulto , Deshidroepiandrosterona/sangre , Enfermedades del Sistema Endocrino/sangre , Epilepsia del Lóbulo Temporal/sangre , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Hipogonadismo/sangre , Hipogonadismo/complicaciones , Hormona Luteinizante/sangre , Trastornos de la Menstruación/sangre , Trastornos de la Menstruación/complicaciones , Quistes Ováricos/sangre , Quistes Ováricos/complicaciones , Prolactina/sangre , Disfunciones Sexuales Fisiológicas/sangre , Disfunciones Sexuales Fisiológicas/complicaciones , Testosterona/sangreRESUMEN
Twenty consecutive men with partial seizures of temporal lobe origin were evaluated for sexual or reproductive dysfunction. Eleven (55%) had diminished sexual interest or reduced potency. Nine of them had reproductive endocrine disorders, with features of hypogonadotropic hypogonadism in five, hyperprolactinemia in two, and hypergonadotropic hypogonadism in two. Among these nine were cases in which the reproductive endocrine abnormalities could not readily be attributed to antiseizure medication use. Other possible interpretations are as follows: epileptic discharges in medial temporal lobe structures may disrupt hypothalamic regulation of pituitary secretion, hypogonadism may promote the development of epileptic discharges, and temporal lobe epilepsy and associated reproductive endocrine disorders may represent the parallel effects of prenatal factors common to the development of both the brain and the reproductive system.
Asunto(s)
Enfermedades del Sistema Endocrino/complicaciones , Epilepsia del Lóbulo Temporal/complicaciones , Adulto , Enfermedades del Sistema Endocrino/sangre , Epilepsia del Lóbulo Temporal/sangre , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Disfunción Eréctil/complicaciones , Hormona Folículo Estimulante/sangre , Humanos , Hiperprolactinemia/complicaciones , Hipogonadismo/sangre , Hipogonadismo/complicaciones , Hormona Luteinizante/sangre , Masculino , Persona de Mediana Edad , Fenitoína/uso terapéutico , Disfunciones Sexuales Fisiológicas/sangre , Disfunciones Sexuales Fisiológicas/complicaciones , Testosterona/sangreRESUMEN
Pseudopregnant rats were injected with either native human chorionic gonadotropin or with (125I)-human chorionic gonadotropin and their ovarian homogenates fractionated on Percoll density gradients. The levels of alpha and beta subunits within subcellular fractions were measured using radioimmunoassays specific for each subunit. Radioactivity measurements of fractions obtained from rats injected with (125I)-human chorionic gonadotropin were used as a separate index of alpha subunit distribution. The alpha subunit was primarily restricted to a combined plasma membrane/prelysosomal vesicle fraction. Immunoreactive beta subunit was present at high concentrations within both this plasma membrane/prelysosomal vesicle fraction and within lysosomes. The striking difference in alpha and beta subcellular distribution may arise from differential sensitivities to lysosomal enzymes.