RESUMO
It has been suggested that menstrual irregularities in hyperprolactinemia are secondary to an increase in hypothalamic dopaminergic activity via a short loop positive feedback of prolactin (PRL). We have studied this question in a relatively new syndrome characterized by hyperprolactinemia without derangements of the hypothalamic-pituitary-ovarian function due to macroprolactinemia (abnormal high amounts of big-big PRL). Central dopaminergic activity was investigated by the administration of the dopamine antagonist domperidone to normal women (n = 7) and women with anovulatory (n = 6) and ovulatory hyperprolactinemia (n = 2). The effects of domperidone were evaluated in all subjects by the measurements of radioimmunoassayable circulating serum PRL and TSH levels. All subjects had a significant increase in serum PRL levels after 90 min of domperidone administration. Anovulatory hyperprolactinemic subjects showed the highest response to domperidone in terms of TSH, whereas normal women and women with ovulatory hyperprolactinemia had similar increments in TSH serum levels after the administration of the dopamine antagonist. These results support the observation that an increase of hypothalamic dopaminergic activity in hyperprolactinemia may account in part for the presence of menstrual irregularities. The presence of a similar pituitary responsiveness in terms of TSH to domperidone in normal and ovulatory hyperprolactinemic women suggests a similar hypothalamic dopaminergic activity in both group of subjects. These findings might offer an explanation for the coexistence of normal ovulatory cycles in spite of hyperprolactinemia.
Assuntos
Domperidona , Hiperprolactinemia/sangue , Prolactina/sangue , Tireotropina/sangue , Adulto , Feminino , Humanos , Hiperprolactinemia/fisiopatologia , OvulaçãoRESUMO
There is enough evidence that prolactin (PRL), like many other pituitary hormones, is composed by multiple forms that differ from each other by size charge. Although they can be seen in the pituitary glands of a variety of species, their biological significance, identity and chemical nature still remain poorly understood. Recently, a new syndrome characterized by normal ovarian function in the presence of sustained hyperprolactinemia has been reported by our group. In these women, highly abnormal percentages of serum big big PRL have been consistently demonstrated. This observation suggests that big big PRL is immunologically similar, but biologically less active than monomeric or little PRL. In this study we have determined then molecular size heterogeneity of immunoreactive PRL in serum and amniotic fluid from two ovulatory hyperprolactinemic subjects (subjects A and B) who had, under non-pregnant conditions, large amounts of serum big big PRL, throughout different stages of parturition. Control subjects consisted of two women at the end of pregnancy in whom PRL species demonstrated a normal size distribution (subjects C and D). Mean basal levels of PRL were the highest in subjects A and B and remained constant during labor. In the control subjects a remarkable decline in PRL levels was observed during the periparturitional period. This pattern of PRL release was not correlated with changes in steroid hormone concentrations. The relative proportions of PRL size variants throughout delivery showed no apparent changes in all four subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Líquido Amniótico/química , Hiperprolactinemia/metabolismo , Ovário/metabolismo , Complicações na Gravidez/metabolismo , Prolactina/química , Adulto , Córion/metabolismo , Estradiol/sangue , Feminino , Humanos , Hiperprolactinemia/fisiopatologia , Peso Molecular , Complicações do Trabalho de Parto/sangue , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/metabolismo , Período Pós-Parto/sangue , Gravidez , Complicações na Gravidez/fisiopatologia , Complicações Neoplásicas na Gravidez/metabolismo , Progesterona/sangue , Prolactina/análise , Prolactina/metabolismo , Prolactinoma/complicações , Prolactinoma/metabolismoRESUMO
We have demonstrated the selective secretion of high mol wt PRL series (big big PRL) in women with hyperprolactinemia and normal ovarian function. This observation suggests that big big PRL is immunologically similar, but biologically less active, than monomeric or little PRL. In this study we determined the molecular size heterogeneity of immunoreactive PRL in the serum from two ovulatory hyperprolactinemic women (subjects A and B) who had large amounts of serum big big PRL during a menstrual cycle and/or gestation. Serum samples obtained throughout the menstrual cycle (days 6, 10, 14, 17, 23, and 28, taking as day 1 the first day of bleeding) and pregnancy (weeks 7, 9, 11, 15, 20, 25, 30, 34, and 38) were fractionated by gel filtration chromatography. PRL was identified in column eluates by specific RIA. Two additional pregnant women, one with a bromocriptine-treated PRL-secreting adenoma (subject C), and a normal woman (subject D) were studied. Big big PRL was the predominant species throughout the different phases of the menstrual cycle in subject B, comprising 70-80% of the total immunoreactive PRL. Most of the remainder was big PRL, and little PRL was present in only small amounts (6-12%) during the luteal phase. During their pregnancies, the serum PRL in subjects A and B initially was mostly big big PRL, but later in gestation the PRL composition shifted from the high mol wt variants to little PRL. The infant's cord (subject A) and peripheral (subject B) serum at birth contained appreciable quantities of big big and big PRL, respectively. These results indicate that structural changes in PRL occur during pregnancy and the menstrual cycle which are probably influenced by the hormonal environment. In addition, the occurrence of larger mol wt PRL species in the serum of the infant of a hyperprolactinemic mother suggests that the presence of high proportions of big big PRL in the serum is genetically determined.
Assuntos
Hiperprolactinemia/sangue , Ciclo Menstrual , Ovário/fisiologia , Gravidez/sangue , Prolactina/sangue , Adulto , Cromatografia em Gel , Estradiol/sangue , Feminino , Sangue Fetal/análise , Humanos , Hiperprolactinemia/genética , Recém-Nascido , Peso Molecular , Progesterona/sangue , Prolactina/genéticaAssuntos
Gonadotropinas Hipofisárias/fisiologia , Esteroides/biossíntese , Adenilil Ciclases/metabolismo , Cálcio/fisiologia , Colesterol/metabolismo , AMP Cíclico/biossíntese , AMP Cíclico/fisiologia , Endocitose , Retroalimentação , Feminino , Glicosilação , Hormônios Esteroides Gonadais/biossíntese , Humanos , Células Intersticiais do Testículo/metabolismo , Lipoproteínas/metabolismo , Masculino , Ovário/metabolismo , Fosfolipídeos/fisiologia , Proteínas Quinases/metabolismo , Receptores da Gonadotropina/metabolismo , Relação Estrutura-Atividade , Testículo/metabolismoRESUMO
Con el objeto de conocer los mecanismos por los cuales el sistema opioíde endógeno (SOE) modula la actividad de la unidad hipotálamo-hipofisiaria, se analizaron los efectos de la administración de clorhidrato de naloxona (NAL) sobre la dinámica gonadotrópica de la hipófisis anterior de la rata macho y hembra durante diferentes estadios de la maduración sexual. A ratas Wistar de ambos sexos (de 5 a 50 días de edad) se les administró NAL por vía subcutánea (10 mg/Kg peso) en 0.05 ml de solución salina. Se utilizaron de 5 a 10 animales por grupo de edad incluyéndose igual número de grupos control los cuales recibieron únicamente 0.05 ml de solución salina. Posterior a una hora de la administración de la NAL, los animales fueron sacrificado colectándose la sangre, así como el hipotálamo y las glándulas hipofisiarias. Las concentraciones en suero y contenido hipofisiario de LH y FSH se determinaron por radioinmunoanálisis específicos. El contenido de receptores hipofisiarios de la hormona liberadora de las gonadotropinas (GnRH) se determinó utilizando el análogo sintético del GnRH, D-Ser(TBu6) -des- Gli10 -GnRH-N- etilamida, el cual fue marcado radiactivamente con I-25 utilizando la técnica enzimática de Lactoperoxidasa. Los cambios producidos por la administración de NAL sobre el procesamiento (cambios post-traduccionales) de FSH hipofisiaria fueron estudiados por cromatografía en concanavalina-A obteniéndose la relación libre y unida de FSH a la lectina. Los resultados demostraron que la inhibición del SOE durante etapas prepuberales induce el incremento de las concentraciones en suero de LH y FSH. Este efecto fue estadísticamente significativo únicamente para el caso de las ratas hembras no observándose efectos importantes en ratas del sexo masculino. El incremento de ambas gonadotropinas estuvo acompañado de la depleción de receptores hipofisiarios para GnRh y del incremento de la fracción libre de la hormona folículo estumulante a nivel hipofisiario...