Effects of prenatal lipopolysaccharide exposure on reproductive activities and serum concentrations of pituitary-gonadal hormones in mice offspring

Maternal infection during pregnancy is a risk factor for some behavioral problems with neurodevelopmental origin. This study aimed to evaluate the effects of exposure of pregnant mice to the bacterial lipopolysaccharide [LPS] on sexual behaviour and serum level of pituitary-gonadal hormones of offspring in adulthood. In this Expremental study, pregnant NMRI mice [n=7/group] were treated with intra-peritoneal administration of LPS [1, 5 and 10 micro g/kg] at day 10 of gestation. Induction of the pro-inflammatory cytokines, Tumor necrosis factor-alpha [TNF-alpha], interleukin-1beta [IL-1beta] and interleukin-6 [IL-6] were measured in maternal serum 2 hours following the maternal LPS challenge. Behavior in the adult male offspring reproductive activity was investigated using receptive female mice. Concentrations of testosterone, luteinizing hormone [LH] and follicle-stimulating hormone [FSH] in adult offspring serum were measured using the enzyme-linked immunosorbent assay [ELISA] method [at postnatal day 60, n=10/group]. One-way ANOVA showed that LPS administration induces a significant increase in TNF-alpha, IL-1beta and IL-6 levels of maternal serum. Prenatal LPS exposure reduces sexual behavior and serum concentration of LH and testosterone in adult male offspring. The overall results suggest that prenatal exposure to LPS increases pro-inflammatory cytokine levels, affects development of neuroendocrine systems and results in the inhibition of reproductive behaviors and reactivity of hypothalamic-pituitary-gonadal [HPG] axis in adult male offspring

Eight years evaluation of children with ambiguous genitalia attending the endocrinology clinic of Alexandria university children's hospital: a retrospective study

Ambiguous genitalia is a real problem in Egypt representing 5.5% of total number of endocrine patients in our study. There is a wide variation of the age at presentation. More than one third of our patients presented with adrenal crisis which is the most serious complication of ambiguous genitalia. Management of cases of DSD requires an experienced multidisciplinary team that is usually found in tertiary centers. Gender assignment in cases of DSD is a difficult challenge. Lack of some laboratory investigations or their higher cost as well as unavailability of some genetic analysis in developing countries are important causes of delayed diagnosis in these cases. The aim of the work was to review the clinical characteristics of children with ambiguous genitalia who attended the endocrinology clinic of Alexandria University Children's Hospital between 2002-2009 to categorize them depending on their clinical, laboratory and radiological findings and to study the response to therapy. All the records of children with ambiguous genitalia who attended the endocrinology clinic in Alexandria University Children's Hospital in the period from 2002 to 2009 were reviewed to obtain data from files regarding history, clinical examination, genital examination and grading, laboratory investigations, karyotyping, radiological findings, laparoscopic findings, final diagnosis, management plan, and gender assignment. This study included 77 children with ambiguous genitalia: Clinically, the sex of presentation was 49 females [63.6%], 21 male patients [27.3%], and 7 cases presented with undetermined sex [9.1%] while according to DSD classification, our patients were classified into 46 XX DSD [79.2%],46 XY DSD [19.5%], and Ovotesticular DSD [only one case]. The age of presentation ranged from 0.23-120 months with a mean of 11.07 +/- 20.03 months. Consanguinity among patient's parents was observed in 36.4%. 39% of our patients presented with adrenal crisis, and 5.2% were associated with other congenital anomalies. 3.8% had pubic hair at presentation and only one case had hypertension. In cases of 46 XXDSD, salt-losing type of congenital adrenal hyperplasia [21-Hydroxylase deficiency] was the commonest type representing 78.7%. In cases of 46 XYDSD, the most frequent diagnosis was androgen insensitivity syndrome that was present in 53.3%. Regarding to gender assignment, 48 cases were reared as females [62.3%] and ten cases were reared as males [13%], the same as their initial sex assignment by their families. 14 cases [18.2%] changed their gender from males to females and five cases [6.5%] had changed from female to male. From our study, we concluded that ambiguous genitalia is a real problem in our country representing 5.5% of total number of endocrine patients in our study. Management of cases of DSD requires an experienced multidisciplinary team that is usually found in tertiary centers. Gender assignment in cases of DSD is a difficult challenge. Lack of some laboratory investigations or their higher cost as well as unavailability of some genetic analysis in developing countries may delay and affects the final diagnosis of some cases of ambiguous genitalia

Serum leptin levels in type-I diabetic children and adolescents versus healthy controls: relationship to age, gender, body mass index, gonadal hormones and pubertal stages

Since childhood and puberty are periods of major metabolic and endocrine changes, the present study was conducted to: [I] Evaluate developmental changes of serum leptin levels in children and adolescents with type-1 diabetes mellitus in comparison with matched healthy controls in respect with chronological age and pubertal stages [2] Evaluate if leptin concentration would be related to obesity observed in children and adolescents with type-1 diabetes during puberty. The study included 60 children diagnosed as type-1 diabetes mellitus by the criteria of American Diabetes Association [ADA] as well as 48 healthy children with matchable age and sex with diabetic patients. The patient and control children were grouped according to their chronological age into 4 groups [6-7yr, 8-10yr, 11-13 yr and 14-16yr] and according to stages of puberty into 3 groups: pre puberty P[1] early puberty P[2] and overt puberty P[3]. Serum leptin levels and BMI were measured to all patients and controls. Also, serum testosterone in boys and serum estradiol in girls were measured by ELISA method. Serum leptin levels significantly increased parallel with age and with pubertal stages both in control and diabetic girls. The maximum levels were observed at 14-16yr age group and at overt stage of puberty. Serum leptin levels were significantly higher in diabetic girls than controls at all studied groups. In control boys, leptin levels were significantly higher at 8-10yr and during P[1] stage then a significant decline occurred thereafter. In contrast, the diabetic boys showed no such decline either with age or with pubertal staging. Diabetic boys had significantly higher leptin levels than control boys at all studied groups. Serum leptin levels in girls were significantly higher than boys either in control or diabetic children. Diabetic children [girls and boys] were significantly older than controls during P[2] and P[3] stage. BMI was significantly increased In diabetic children [girls and boys] than controls during P[1], P[2] and P[3] stage whereas serum estradiol in diabetic girls and testosterone in diabetic boys were significantly lower than controls during P[2] and P[3] stages. Significant positive correlations were observed between serum leptin levels versus age, BMI and estradiol hormone in control girls. Also significant positive correlations were found in diabetic girls between serum leptin levels and each of age, BMI and estradiol hormone. In control boys significant negative correlations were observed between serum leptin level and each of age and testosterone hormone whereas non significant with BMI. Significant positive correlations were found in diabetic boys between serum leptin levels and each of age and BMI, while the correlation with testosterone was non significant. In conclusion leptin appears to participate in various endocrinological and physiological process in human body. Among the more notable are obesity and pubertal delay-associated diabetes. Thus, it may be involved in regulation of body weight and signaling the onset of puberty and maintenance of reproductive function thereafter

Molecular genetic and biochemical evaluation of ghrelin hormone as a novel signal of gonadal function in adult male rats

It is well known that reproductive function is regulated by the interplay of the hypothalamus, pituitary and gonads, which form the so called reproductive axis. A number of factors primarily involved in the control of energy balance and metabolism have been proven as putative modulators of the gonadal axis, thus providing the basis for the link between energy homeostasis and fertility. Ghrelin is a 28 amino acid peptide. It is predominantly produced by the endocrine X/ A- like cells of the stomach submucosa and mobilized by food deprivation. Ghrelin concentrations were observed to change with fasting and refeeding in mammals. The potential reproductive role of ghrelin has received attention recently. The Objective of this work is to study the effect of chronic food restriction on ghrelin level in adult male rats and it's relation to reproductive hormones. The present study was carried out on 32 adult male Sprague Dawley rats divided into 4 groups: Group I [control group] comprised 8 rats fed ad libitum for 30 days, Group II, III and IV [food-restricted groups for 10, 20 and 30 days respectively] each consisted of 8 rats fed 50% of ad libitum intake determined by the amount of food consumed by the control group. Mean body weight of food restricted rats was observed to decrease during the period of the experiment. Food restriction produced significant increase of serum ghrelin with significant decrease of both gastric and hypothalamic ghrelin accompanied with significant increase in its gene expression in stomach and hypothalamus. Testosterone, follicle- stimulating hormone [FSH] and luteinizing hormone [LH] levels showed significant decrease correlated with down- regulation of gonadotropins, aromatase and kisspeptin [Kissl] genes in food restricted rats compared with control group. Ghrelin could be one of the hormones responsible for the suppression of male reproductive axis in case of negative energy balance. Thus, ghrelin could provide a link between energy homeostasis and reproductive capacity in adult male rats

Efeito da hiperprolactinemia induzida pela metoclopramida na córnea de camundongas / Effects of metoclopramide-induced hyperprolactinemia on the murine corneal

OBJETIVO: Avaliar as alterações morfológicas promovidas pela hiperprolactinemia induzida pela metoclopramida na córnea de camundongas durante a fase de proestro e na gestação. MÉTODOS: Quarenta camundongas adultas foram divididas, aleatoriamente, em dois grupos, a saber: controle (CTR1) e metoclopramida (MET1). Após 50 dias metade dos animais de cada grupo foram sacrificados. O restante dos animais foi acasalado, constituindo dois grupos: controle prenhe (CTR2) e o metoclopramida prenhe (MET2), que foi sacrificado no 6° dia de gestação. Após decapitação dos animais coletou-se sangue para dosagens de estradiol, progesterona e prolactina, em seguida removidos os globos oculares para estudo histomorfométrico da córnea. RESULTADOS: As espessuras do epitélio, estroma, endotélio e a espessura total das córneas dos grupos experimentais: MET1 e MET2 mostraram-se mais espessados quando comparados com os grupos controles: CTR1 e CTR2, respectivamente. Houve redução dos níveis hormonais do estrogênio e da progesterona nos animais que receberam metoclopramida em comparação com os respectivos controles (CTR1: estradiol = 156,6±42,2 pg/ml; progesterona = 39,4±5,1 ng/ml; prolactina = 130,4±26,2 ng/ml; MET1: estradiol = 108,0±33,1 pg/ml; progesterona = 28,0±6,4 ng/ml; prolactina = 551,5± 23,3 ng/ml; CTR2: estradiol = 354,0±56,0 pg/ml; progesterona = 251,0± 56,0 ng/ml; prolactina = 423,2±28,1 ng/ml; MET2: estradiol = 293,0± 43,0 pg/ml; progesterona = 184,0±33,0 ng/ml; prolactina = 823,1±51,1 ng/ml). CONCLUSÃO: A hiperprolactinemia induzida pela metoclopramida produziu espessamento da córnea, sobretudo, em camundongas prenhes. Possivelmente este efeito está relacionado com a redução da produção hormonal de estrogênio e de progesterona.

PURPOSE: To evaluate the morphological changes in murine cornea upon metoclopramide-induced hyperprolactinemia during the proestrous phase or pregnancy. METHODS: Forty adult mice were divided into two groups: (control) CTR1 and (treated with metoclopramide (MET1). After fifty days, half of the mice were sacrificed. The remaining animals were mated, and then labeled as pregnant controls (CTR2). Part of these animals were treated with metoclopramide and constituted the metoclopramide-treated pregnant (MET2) group. The groups CTR2 and MET2 were sacrificed on the 6th day of pregnancy. The hormonal levels were assessed by chemioluminescence and radioimmunoassay methods and the cornea was removed for the histomorphometric study. RESULTS: The epithelial, stromal, endothelial and total thickness in the experimental group was: MET1 and MET2 were higher than one in the control group: CTR1 and CTR2. There was a significant reduction of the hormonal level in the animals that received metoclopramide as compared to controls (CTR1: estradiol = 156.6±42.2 pg/ml; progesterone = 39.4±5.1 ng/ml; prolactin = 130.4±26.2 ng/ml; MET1: estradiol = 108.0±33.1 pg/ml; progesterone = 28.0±6.4 ng/ml; prolactin = 551.5±23.3 ng/ml; CTR2: estradiol = 354.0±56.0 pg/ml; progesterone = 251.0±56.0 ng/ml; prolactin = 423.2±28.1 ng/ml; MET2: estradiol = 293.0±43.0 pg/ml; progesterone = 184.0±33.0 ng/ml; prolactin = 823.1±51.1 ng/ml). CONCLUSION: The metoclopramide-induced hyperprolactinemia may increase corneal layers, mainly in pregnant mice. Possibly, this effect is related to reduction in estrogen and progesterone production.