Transient central precocious puberty: a new entity among the spectrum of precocious puberty?

OBJECTIVE: Recently, we observed some cases of Precocious Puberty (PP) with a partial central activation of hypothalamic-pituitary-gonadal (HPG) axis that tended to normalized in 6-12 months. To evaluate the frequency of this form within the spectrum of forms of PP, we retrospectively assessed the clinical, hormonal and ultrasound characteristics of patients attending to our Center for signs of PP, between 2007 and 2017. To hypothesize some causes of this "pubertal poussée" a questionnaire about environmental data was provided to patients. METHODS: 96 girls were recruited for the study and divided into three Groups. Group 1: 56 subjects with Central PP (CPP) requiring treatment with GnRH analogue; Group 2: 22 subjects with transient activation of pubertal axis, that tended to normalize, "Transient CPP"(T-CPP); Group 3: 18 subjects with Isolated Thelarche (IT). RESULTS: Mean age at diagnosis was 6.8 ± 1.0 years in Group 1, 5.9 ± 1.3 years in Group 2 and 5.6 ± 1.5 years in Group 3. A significant increase of diagnosis of T-CPP was observed over the study period. Significantly higher use of some homeopathic medicines and potential exposure to pesticides was reported in Group 2 vs Group 1. CONCLUSIONS: To our knowledge, we first reported a form defined as T-CPP, characterized by partial activation in the HPG axis normalizing over time. An increased use of homeopathic medicines and exposure to environmental pollutants in these patients was evidenced.

[Effect of the Yifuning soft gelatin capsules on estrogen receptor and nitric oxide levels in ovariectomized rats].

OBJECTIVE: To investigate the effects of the Yifuning soft gelatin capsules(YFN)on estrogen receptor (ER) and nitric oxide (NO) levels in ovariectomized rats. METHOD: Fifty female mature sprague-dawley rats were randomly divided into 5 groups: normal control; model control; diethylstilbestrol tablets (DT); YFN (high dose and low dose). After 4 weeks' treatment, the serum E2 levels were detected by radioimmunoassay. The estrogen receptor (ER) levels of uterus and artery were detected with method of radioligand binding assay of receptor (RBAR). The uterus pathologic changes were investigated with light microscope. NO and NOS levels of the artery and the uterus index were detected too. RESULT: YFN can obviously improve serum E2, increase index and ER of uterus (P < 0.01 or P < 0.05), and ameliorate the uterus' pathologic changes in OVX rats. It also can increase the artery' ER, NO and NOS levels. CONCLUSION: YFN can cure the climacteric syndrome and prevent the cardiovascular disease after post-menopause.

Demonstration of progesterone receptors in rat Schwann cells.

We have recently shown that progesterone promotes myelin formation in peripheral nerves of rodents. In this study, we demonstrate the presence of progesterone receptors (PR) in primary cultures of rat Schwann cells, the glial cells of the PNS, prepared from sciatic nerves of 4-5 days old rats. After 3 weeks of culture, the presence of PR was measured by whole cell assay after incubating living cells for 1 h at 37 degrees C with [3H]-Organon 2058 as a ligand, and about 5000 specific binding sites per cell were found. In contrast to the PR of rat glial cells from the central nervous system (CNS), which is induced by estrogens, treatment of Schwann cells with estradiol did not increase the PR-binding, even after exposure of cells to high doses of estrogen under various culture conditions. Progesterone receptors were also visualized in Schwann cells by indirect immunofluorescence staining with a monoclonal anti-PR antibody. Again, treatment of the cells with estradiol did not increase the immunofluorescence staining of the PR. Specific PR binding was also measured in sciatic nerves of adult female rats. Cytosol was prepared and labeled with [3H]-Organon 2058 for 15 h at 2 degrees C. After treatment with dextran-coated charcoal, specific ligand binding was about 30 fmol/mg cytosolic protein. When castrated adult female rats were treated with estradiol (20 micrograms EB/day for 3 days), no PR-induction was observed in the cytosol of sciatic nerves. In contrast, PR-binding sites in cytosols prepared from pituitary gland and uteri of the same animals were significantly increased by the estrogen.

Kinetic analysis of the binding of nomegestrol acetate to the progesterone receptors in rat uterus by competition studies.

The characteristics of binding (Kinetic and equilibrium binding analysis) of nomegestrol acetate (NOM, 17 alpha-acetoxy-6 alpha-methyl-19-nor-pregna-4.6-diene-3.20-dione) to the progesterone receptor (PgR) in rat uterine cytosolic fraction were determined in comparison to progesterone (P), to fully appreciate the amplitude and specificity of the induced biological response. Since an appropriate radio-labelled form of this steroid molecule was not available, competition studies were performed against the synthetic progestin: [3H]-Organon 2058 [( 3H]-ORG). This allowed a direct comparison between the unlabelled forms of NOM and P, the kinetic constants of which were respectively: Inhibition constant (Ki): 22.8 and 34.3 nM; Association rate constant (k1): 0.39 X 10(3) and 0.21 X 10(3) M-1.s-1; Dissociation rate constant (k-1): 1.81 X 10(-5) and 2.16 X 10(-5) s-1. These results are much more informative than the mere determination of relative binding affinities which only reflect the specificity of the PgR. It was concluded that NOM behaves like the natural hormone in the cytosol of rat uterus.

Effect of oviductus ranae and oviductus ranae eggs on bone metabolism and osteoporosis.

OBJECTIVE: To evaluate the roles or effects of oviductus ranae (OR) or oviductus ranae eggs (ORE) in preventing and treating postmenopausal osteoporosis. METHODS: In vivo experiment: Sixty female adult Wistar rats were randomly divided into 5 groups of 12. To provide an osteoporosis model 4 groups of rats were ovariectomized (OVX), with the 5th being sham operated. Medication commenced 7 days after the operation and lasted continuously for 12 weeks. Sham operated and OVX groups were given equivalent volumes of 5% Tween-80. The other three groups intragastrically received conjugated estrogens (CE), OR or ORE of the corresponding doses. At the 12th week, serum estrogen, bone gla protein (BGP), serum calcium, phosphorus, and alkaline phosphatase (ALP) were assayed; bone mineral densities (BMD) were measured and bone scanning was conducted; uteri were weighed, and weight, volume and length of the femoral bones were determined; and cortical thickness of femoral heads and area of bone trabecula were measured by image analyzer. In vitro experiment: Eighty 10-month old SD rats, with equal numbers of males and females, were randomly divided into 8 groups. Osteoblasts were isolated from neonatal rat calvariae, and the cells were exposed to various concentrations of serum from OR and ORE groups to study the impact of these sera on osteoblastic proliferation, ALP activity and mineralization. Osteoclastic numbers were determined using tartrate resistant acid phosphatase (TRAP). RESULTS: In vivo experiment: The body weight of the four OVX groups increased significantly (P<0.01). Uterine weight of the CE group was the highest (P<0.01); Compared with the model group, estrogen level, BMD, bone scanning/bone imaging index weight of the femoral bones, cortical thickness of femoral heads in the OR and ORE groups increased significantly (P<0.05, P<0.01); femoral volume in the ORE group increased significantly (P<0.05); and the content of osteocalcin, phosphorus, and ALP in serum decreased significantly (P<0.05, P<0.01). In vitro experiment: Sera from OR and ORE groups had notable effects on the proliferation of osteoblasts (P<0.05 and P<0.01, repsectively) and stimulated the formation of calcium nodes (P<0.05, P<0.01), while the enhancement of ALP activity in osteoblasts was significant (P<0.05, P<0.01). The number of TRAP-positive cells was significantly reduced as well (P<0.01). CONCLUSIONS: OR and its eggs could effectively suppress OVX-induced osteoporosis in rats, and increase bone turnover possibly by both an increase in osteoblastic activity and a decrease in osteoclastic activity. The present study provides evidence that OR and its eggs could be considered a complementary and alternative medicine for the treatment of postmenopausal osteoporosis.

Effects of Chinese Materia Medica-Fubao Danggui Jiao on experimental endometriosis.

The objective of this paper was to investigate the effects of a Chinese Materia Medica variant -Fubao Danggui Jiao (FDJ)-on experimental endometriosis. An endometriosis model was created by virtue of auto-transplantation of endometrial tissue onto rats' abdominal walls. The implants were allowed to grow for 30 days until the successful completion of the model. After that, forty endometriotic rats were randomly divided into four study groups and given different treatments: (1) negative control group (water, 2ml/kg, per os); (2) FDJ-A group (FDJ, 2ml/kg, per os); (3) FDJ-B group (FDJ, 4ml/kg, per os); (4) Danazol group (70mg/kg, per os). After 30 days with treatments, the volumes of endometriotic implants in each rat were measured. The implants and normal uterine horns were removed for routine histological examination. FDJ caused significant decreases in volumes of the surviving endometriotic implants, with two different doses having statistically equivalent effects. Upon histological examination, FDJ was observed to cause regression of epithelium and stroma of endometriotic implants. FDJ had revealed promising therapeutic effects on endometriosis.

[Protective effect of Oviductus Ranae capsules on the reproductive organs of aged mice].

OBJECTIVE: To observe the protective effect of Oviductus Ranae (OR) capsules on the reproductive organs in an aged mouse model established by D-galactose injection. METHODS: Forty-eight female Kunming mice were randomly divided into 4 equal groups, namely the high- and low-dose OR groups, diethylstilbestrol (DT) group, and model group. The mice received subcutaneous injection of D-galactose for 6 weeks to establish aging models. Another 12 mice were injected daily with normal saline (NS) to serve as the normal control group. From the third week of the experiment, the mice were given oral OR at low or high doses (in the OR groups) or vegetable oil (in the model or control groups) till the sixth week. In the last two weeks, the vaginal smears were obtained from the mice for evaluating the changes of the vaginal keratinocytes and counting the days of estrus. After completion of drug administration, all the mice were sacrificed and the serum content of estradiol (E(2)) was detected by radioimmunoassay, with the ovarian and uterine indices determined. The ovarian and uterine pathologies were observed using HE staining, and SOD and MDA activities in the ovary and uterus were also assessed. RESULTS: OR obviously increased E(2) level and the ovarian and uterine indices in the aged mice, also alleviating the pathological change of the ovary and uterus. OR substantially depressed MDA content and enhanced SOD activity in the ovary and uterus. CONCLUSION: OR has definite antioxidative effects and ameliorates the degenerative changes of the reproductive organs in mouse models of aging.

Comparison of uterine concentrations of ethinyl estradiol and etonogestrel after use of a contraceptive vaginal ring and an oral contraceptive.

OBJECTIVE: To compare uterine tissue concentrations of ethinyl estradiol (EE) and etonogestrel (ENG) after one cycle of use of a contraceptive vaginal ring (NuvaRing; NV Organon, Oss, The Netherlands) or a combined oral contraceptive (COC). DESIGN: Randomized, open-label, pharmacokinetic study. SETTING: Obstetrics and gynecology unit. PATIENT(S): Eight premenopausal women about to undergo hysterectomy but otherwise healthy. INTERVENTION(S): One cycle (17-21 days) of NuvaRing or COC treatment that ended with surgical hysterectomy. MAIN OUTCOME MEASURE(S): Tissue concentrations of EE and ENG in uterine tissue samples taken from the upper myometrium and mid-myometrium, the cervical region, and the endometrium. RESULT(S): In both groups, concentrations of EE and ENG were similar in uterine tissue taken from the upper myometrium and mid-myometrium and the cervical region. However, compared with the COC group, concentrations of both hormones were markedly lower in tissue samples from the endometrium of women who had been treated with NuvaRing. CONCLUSION(S): Vaginal administration of hormones with NuvaRing did not produce elevated uterine concentrations of EE and ENG, compared with an oral contraceptive.

Conduta frente às malformações genitais uterinas: revisão baseada em evidências / Medical care for uterine genital malformations: evidence-based review

Este trabalho de revisão foi idealizado para analisar as malformações dos ductos de Müller, que, devido à sua frequência de 3 a 7,3% na população em geral, justificam uma análise mais profunda do tema. O objetivo foi avaliar, de acordo com a literatura por meio de metodologia adequada? Os aspectos mais relevantes dessas anomalias, com destaque para a etiopatogenia, classificação, diagnóstico e tratamento. Os resultados obtidos nesta revisão apontaram as melhores evidências, até o momento, de como conduzir as mulheres portadoras dessas malformações.

This review paper was organized in order to analyse Müllerian anomalies, because their frequency from 3 to 7,3% in people in general justify a better evaluation about these malformations. The objective of the study was to evaluate, according to literature - by a proper methodology - the main aspects of these malformations, with special attention to etiology, classification, diagnostic and treatment. The results of this review showed the best evidences up till now of how to manage women with these genital malformations.

Gonadotropin-releasing hormone specific binding sites in uterine leiomyomata.

Gonadotropin-releasing hormone (GnRH) analogs can cause regression of uterine leiomyomata. This effect is thought to be mediated by the inhibition of gonadotropin release and steroid synthesis. In the present study we examined the possibility that these analogs may also act directly on uterine leiomyomata. Specific binding sites for GnRH are present in myoma membranes, as 125I-Buserelin binding was displaced with equal efficiency by the superagonists, Buserelin and D-Trp6-GnRH, and by the antagonist Organon 30276, but not by unrelated peptides such as thyrotropin releasing hormone and oxytocin. A nonlinear Scatchard curve obtained for Buserelin specific binding suggests the presence of at least two binding sites, one of which exhibits a relatively high affinity for GnRH analogs (Kd of approximately 10(-8) M). Western blotting with a specific GnRH receptor antibody revealed the presence of a 60 kDa protein in myoma membranes. This protein has a similar molecular weight to the purified pituitary GnRH receptor. These results indicate, for the first time, the presence of specific binding sites for GnRH in uterine leiomyomata, suggesting a direct effect of GnRH analogs on this tissue.

Interaction of some traditional plant extracts with uterine oestrogen or progestin receptors.

Previous work has demonstrated that stem bark extracts of Combretodendron macrocarpum (Barringtoniaceae), Cola nitida (Sterculiaceae), Afrormosia laxiflora and Pterocarpus erinaceus (Fabaceae) blocked the oestrus cycle of female rats through antigonadotropic activity. Moreover, a study of the plant substances responsible for these effects revealed the presence of phyto-anti-oestrogens in these plant extracts. In order to explain the mechanism by which these substances exert their antifertility actions, the interaction of the plant extract with oestrogen and progesterone receptors was studied. All crude extracts exerted inhibition of ((3)H)-oestradiol or ((3)H)-Organon binding to their respective receptors but their relative affinities were much lower than those of oestradiol or progesterone. Respective efficiencies of plant extracts in competing for the oestrogen receptor were as follows: A. laxiflora > P. erinaceus > C. macrocarpum > C. nitida. The efficiency order of competition for the progestin receptor was different to that of oestrogen. The most potent competitor was C. macrocarpum extract, followed by P. erinaceus, C. nitida and A. laxiflora. Moreover, the interaction between oestradiol and plant extracts with the oestrogen receptor was determined to be competitive only for C. macrocarpum and A. laxiflora, whereas all compounds produced a competitive inhibition on the progestin receptor binding. These results suggest that the plant extract binding site was the same site as for the steroid. These results suggest also that crude plant extracts may interfere with natural oestrogen and/or progestagen in vivo by binding to steroid receptors.