RESUMO
Growth hormone (GH) and prolactin share similarities in structure and function. We have previously shown that women with congenital isolated GH deficiency (IGHD) caused by a homozygous mutation in the GHRH receptor gene (GHRHR) (MUT/MUT) have a short reproductive life, with anticipated climacteric. At climacteric, they have lower prolactin levels than normal controls (N/N). Because they are able to breast feed, we hypothesized that this prolactin reduction is limited to climacteric, as result of lower estradiol exposure of the lactotrophs. The purposes of this work were to assess prolactin levels in broader age adults homozygous and heterozygous (MUT/N) for the mutation and in normal controls (N/N), and to correlate them to sex steroids levels. We enrolled 24 GH-naïve MUT/MUT (12 female), 25 MUT/N (14 female), and 25 N/N (11 female) subjects, aged 25-65 years. Anthropometric data and serum prolactin, estradiol, total testosterone, and sex hormone binding globulin (SHBG) were measured. Free testosterone was calculated. Prolactin levels were similar in the three groups. In males, testosterone and SHBG levels were higher in MUT/MUT in comparison to N/N. There was no difference in free testosterone among groups. In all 74 individuals, prolactin correlated inversely with age (p < 0.0001) and directly with serum estradiol (p = 0.018). Prolactin levels in subjects with IGHD due to a homozygous GHRHR mutation are similar to heterozygous and normal homozygous, but total testosterone and SHBG are higher in male MUT/MUT, with no difference in free testosterone. The reduced prolactin level is limited to climacteric period, possibly due to reduced estrogen exposure.
Assuntos
Nanismo Hipofisário/sangue , Hormônios Esteroides Gonadais/sangue , Prolactina/sangue , Adulto , Idoso , Estudos de Casos e Controles , Nanismo Hipofisário/epidemiologia , Nanismo Hipofisário/genética , Feminino , Humanos , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Receptores de Neuropeptídeos/genética , Receptores de Hormônios Reguladores de Hormônio Hipofisário/genética , Globulina de Ligação a Hormônio Sexual/análiseRESUMO
Ao envelhecer, a mulher passa por uma série de alterações endócrinas e físicas devido à diminuição da secreção de esteroides ovarianos. Consequentemente, ocorre atrofia dos caracteres sexuais secundários, diminuição da massa óssea e aumento do risco de doenças cardiovasculares. Desde que a diminuição dos níveis plasmáticos de estrógeno foi relacionada ao sistema neuroendócrino, que interfere diretamente no humor, comportamento e cognição, passou a ser aceitável que mulheres com história de depressão, ainda na menacme, podem ter um comprometimento de longa data no eixo hipotálamo-hipófise-ovariano. Somam-se ao climatério os sintomas da tensão pré-menstrual, que acometem a maioria das mulheres em idade reprodutiva, cerca de 75 a 80%. Entre 2 e 8% das mulheres em idade reprodutiva sofrem sintomas graves o suficiente para desestruturar as vidas social e familiar e/ou profissional durante uma ou duas semanas de cada mês. Desde o momento em que se inicia o declínio da função ovariana, alguns anos antes da ocorrência da menopausa, até o fim da vida, ocorrem modificações biopsicossociais de maneira insidiosa e de forma variável em cada mulher.
A woman goes through a series of physical and endocrine changes due to decreased secretion of ovarian steroids with aging. Consequently, atrophy of secondary sex characteristics, decrease in bone mass and increase in the risk of cardiovascular diseases are present. Since the decrease in plasma levels of estrogen was related to the neuroendocrine system, which interferes directly with mood, behavior and cognition, it is acceptable for women with history of depression, even in premenopausal age, to have a lasting hypothalamus-pituitary- ovarian involvement, in addition to climacteric symptoms of premenstrual syndrome, which affects the majority of women (75-80%) in reproductive age. From 2 to 8% of women in their reproductive age suffer from symptoms severe enough to interfere with their social, familial and business lives during one or two weeks each month. When decline of ovarian function occurs a few years before the onset of menopause until the end of life recurrent and variable biopsychosocial changes occur in women.
Assuntos
Humanos , Feminino , Climatério , Pré-Menopausa , Síndrome Pré-MenstrualRESUMO
OBJECTIVE: To study the time, intensity of symptoms, hormonal profile, and related morbidity of climacteric in women with untreated isolated growth hormone (GH) deficiency (IGHD). DESIGN: Women belonging to a large Brazilian kindred with IGHD due to a homozygous mutation in the GH-releasing hormone receptor gene were studied. None of them had ever received GH replacement therapy. A two-step protocol was performed. In the first case-control experiment, aimed to determine the age at climacteric, we compared eight women with IGHD and 32 normal women between 37 and 55 years of age. In the second cross-sectional experiment, aimed to determine the severity of climacteric symptoms, seven women with IGHD (aged 47-65 y) were compared with 13 controls (aged 44-65 y). The Kupperman Index scores, serum follicle-stimulating hormone, luteinizing hormone, prolactin, and estradiol levels were determined, and pelvic and mammary ultrasonography, mammography, and colpocytology were performed. RESULTS: The number of women with follicle-stimulating hormone above 20 mIU/mL was higher in women with IGHD than controls. Kupperman's Index was not different between the two groups. Menarche had been delayed and parity was lower in women with IGHD. Hormonal profile was similar, but prolactin was lower in women with IGHD. Uterine volume was smaller in women with IGHD, and endometrial thickness and ovarian volume were similar in the two groups. No difference in breast images or in colpocytology was observed between the two groups. CONCLUSIONS: Menarche was delayed and the beginning of climacteric is anticipated in untreated lifetime IGHD, but menopausal symptoms and hormonal profile resemble the normal climacteric.
Assuntos
Climatério , Nanismo Hipofisário/fisiopatologia , Hormônio do Crescimento Humano/deficiência , Adulto , Idoso , Nanismo Hipofisário/sangue , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Pessoa de Meia-Idade , Prolactina/sangueRESUMO
OBJECTIVE: To assess the sizes of intra-abdominal organs of adult subjects with untreated severe congenital isolated GH deficiency (IGHD) due to lack of functional GHRH receptor (GHRH-R), and to verify whether there is proportionality between size of organ and adult stature and body surface area (BSA). SUBJECTS AND METHODS: By using ultrasound, we studied the sizes (absolute and corrected by height, weight and BSA) of the intra-abdominal organs of 18 adult subjects with IGHD (eight females, IGHD group) who have never received GH replacement therapy. They were all homozygous for the same null mutation (IVS1 + 1G --> A) in the GHRH receptor gene (GHRH-R). They were compared with normal controls from the same region. RESULTS: After correction for BSA, subjects lacking a functional GHRH-R have normal prostate and ovaries size, small spleen and uterus, and large liver, pancreas and kidney. CONCLUSIONS: Size of individual abdominal organs is influenced in different ways by severe and congenital lack of GH due to a GHRH-R mutation.