Endochondral ossification of hindlimbs in embryonic development of Japanese Quail(Coturnix japonica)

The endochondral ossification of hindlimb is essential to a bird’s ability to stand,walk and fly.Most hindlimb is ossified in the embryos before hatching in precocial birds.However,the molecular mechanisms of hindlimb ossification in birds is still unclear.Therefore,we tried to examine the process of hindlimb ossification and its molecular regulation by using an animal model—Japanese Quail(Coturnix japonica).We selected four critical stages(Embryo Day:E6,E8,E12 and E16) of skeletal development of embryonic quails for hindlimb skeleton staining to show the process of endochondral ossification and to examine the molecular regulation of endochondral osteogenesis by RNA-Seq analysis.The results showed that ossification became increased with embryonic development and most hindlimb was ossified before hatching.RNA-Seq analysis revealed that various signaling pathways were involved with endochondral ossification with thyroid hormone signaling and WNT signaling pathway particularly enriched.Moreover,the expression levels of 42 genes were continuously upregulated and 14 genes were continuously downregulated from E6 to E16.The present study might provide new insights into complex molecular mechanisms in regulation of endochondral ossification.

Incubation temperature induced developmental plasticity of cold responsive physiological phenotypes in Japanese Quails

Embryonic development is a critical period for phenotype formation.Environmental variation during embryonic development can induce changes in postnatal phenotypes of animals.The thyroxine secretion and aerobic metabolic activity of small birds are important phenotypes closely related to their winter survival.In the context of climate change,it is necessary to determine whether temperature variation during incubation in birds leads to developmental plasticity of these cold responsive phenotypes.We incubated Japanese Quail(Coturnix japonica)eggs at 36.8℃,37.8℃,and 38.8℃,and raised the chicks to 35-day old at 22℃with same raising conditions,then all the quails were exposed to gradually temperature dropping environment(from 15℃to 0℃).After cold treatment,serum T3 level,resting metabolic rate,skeletal muscle and liver metabolomes of the birds were measured.The serum T3 levels were significantly lower in the 38.8℃group and significantly higher in the 36.8℃group compared to the 37.8℃group.The metabolic rate in the 38.8℃group was significantly lower compared to the 37.8℃group.Compared with the 37.8℃group,metabolites involved in the tricarboxylic acid cycle in the liver were significantly lower in the 38.8℃group,and metabolites related to lipid oxidation metabolism and fatty acid biosynthesis were significantly lower in the skeletal muscles in the 38.8℃group but significantly higher in the 36.8℃group.These results indicate that incubation temperature variation can lead to developmental plasticity in cold responsive physiological phenotypes.Higher incubation temperature may impair the capacity of birds coping with cold challenge.

Effect of dietary with Zhibai dihuang pills and gonadotropinreleasing-hormone-analogue on girls with precocious and rapidly progressive puberty

BACKGROUND At present,the clinical mechanisms underlying precocious puberty remain unclear,making effective intervention for children experiencing this condition and rapidly progressive puberty essential.AIM To explore the effects of Zhibai dihuang pills and gonadotropin-releasing hormone analogue(GnRHa)on growth and ovarian function in girls with precocious puberty.METHODS The clinical data of 84 adolescent girls with precocious puberty and rapidly progressive puberty from February 2017 to August 2023 were retrospectively analyzed.Girls were divided into a control group and an observation group,with 42 cases in each group.The control group received diet intervention combined with GnRHa treatment,while the observation group received diet intervention combined with Zhibai dihuang pills+GnRHa treatment.Outcomes such as clinical efficacy,growth indicators,ovarian function,and adverse reactions were compared between the two groups.RESULTS The observation group showed superior clinical efficacy compared to the control group(P<0.05).Prior to the intervention,no significant differences were found in growth or ovarian function between the groups(P>0.05).Post-intervention,the observation group exhibited significantly lower rates in growth,height,and bone age,along with reduced levels of progesterone,testosterone,estradiol,prolactin,luteinizing hormone,and follicle-stimulating hormone compared to the control group(P<0.05).The incidence of adverse reactions was similar across both groups(P>0.05).CONCLUSION Combining Zhibai dihuang pills with GnRHa and dietary intervention effectively improves growth,enhances ovarian function,and minimizes adverse reactions in adolescent girls with precocious and rapidly progressive puberty.

Treatment of central precocious puberty by GnRH analogs： long-term outcome in men

In boys, central precocious puberty （CPP） is the appearance of secondary sex characteristics driven by pituitary gonadotropin secretion before the age of 9 years. In the last years, relevant improvements in the treatment of CPP have been achieved. Because CPP is rare in boys, the majority of papers on this issue focus on girls and do not address specific features of male patients regarding end results and safety. In the present paper, recent advances of CPP management with GnRH analogs in men are summarized. End results in untreated and treated patients are also reviewed by an analysis of the recently published literature on treatment of CPP in men. The available data indicate that therapy with GnRH analogs can improve final height into the range of target height without significant adverse short-term and long-term effects, but longer follow-up of larger series of patients is still required to draw definitive conclusions.

Expression and significance of netrin-1 and its receptor UNC5C in precocious puberty female rat hypothalamus

Objective:To study expressions of netrin-1 and its receptor UNC5 C in female precocious puberty rat hypothalamus,and explore its effect on precocious puberty process.Methods:Forty female one-week-old SD rats were randomly divided into four groups:experimental group A(precocious puberty early youth),experimental group B(precocious puberty medium youth),group A(normal pre-puberty).group B(normal early youth) with 10 rats in each group.Precocious puberty experimental rats were induced with Danazol and rals in control group were injected with saline.Uterus and ovaries were removed,specimens were weighed,litems index and ovarian index were calculated,and amount of luteinizing hormone(LH) and follicle-stimulating hormone(FSH) were detected from the blood by ELISA.Real-time PCR was used to delect netrin-1 and its receptor UNC5 C.as well as hypothalamic gonadolropinreleasing hormone(GnRH) mRNA expression in hypothalamus tissues:and then,a coimmunoprecipitation study of interactions between netrin-1 and its receptor UNC5 C was carried out.Results:Relative target gene expression levels of control group A,control group B.experimental group A,and experimental group B(with,3-actin as an internal control for normalization) were as follows:Netrin-1:3.5±0.9,5.4±0.7.4.9±1.0.5.3±0.3:UNC5C:0.8±0.04.1.7±0.2.1.82±0.23.1.58±0.4:GnRH:1.2±0.3.2.7±0.3.2.4±0.7.3.2±0.4.Conclusions:LH and FSH concentrations,netrin-1 and its receptor expression are increased in precocious puberty animal models.

Regulative Actions of the Chinese Drugs for Tonifying the Kidney on Gene Expression of the Hypothalamic GnRH,Pituitary FSH,LH and Osteoblastic BGP

It is found that the drugs for nourishing yin to reduce pathogenic fire can significantly down-regulate,and the drugs for tonifying the kidney to replenish essence can up-regulate mRNA expression of the hypothalamic GnRH,pituitary FSH,LH and osteoblastic BGP,indicating that the Chinese drugs for tonifying the kidney can regulate gene expression of the hypothalamic GnRH,pituitary FSH,LH,and osteoblastic BGP,which is possibly one of the main mechanisms of the Chinese drug for tonifying the kidney,regulating ephebic development process and improving skeletal development in sexual precocity children.

Efficacy of Subcutaneous Administration of Gonadotropin-releasing Hormone Agonist on Idiopathic Central Precocious Puberty

In order to assess the feasibility of subcutaneous administration of Triptorelin with 6-week intervals for the suppression of pituitary-gonadal axis and changes of clinical signs in girls with idiopathic central precocious puberty （ICPP）, 46 girls with ICPP were treated with GnRHa. Triptorelin （Decapeptyl, 3.75 mg） was administered subcutaneously （SC） at 6-weeks intervals or intramuscularly （IM） at 4-weeks intervals randomly for more than 12 months consecutively. During GnRHa therapy, clinical parameters and laboratory data, including height, weight, pubertal stage, bone age, uterine volume and ovarian size, serum levels of luteinizing hormone （LH）, follicle stimulating hormone （FSH） and estradiol （E2）, were monitored and analyzed. It was found that both treatment regimes led to regression of precocious puberty and reversal of secondary sexual characteristics. Breast developments regressed. Uterine volume was decreased after treatment, but there was no statistically significant difference. Mean ovarian volume did not change significantly during treatment. The height velocity was decreased significandy from 6.3±1.4 cm/year to 5.8：1：1.2 cm/year in group SC and 6.7±1.3 cm/year to 5.4±1.0 cm/year in group IM, respectively. The rate of bone maturation was reduced significantly during treatment. The ratio of deltaBAgdeltaCA was 1.2±0.2 or 1.3±0.3 at the onset of therapy and decreased significantly after the treatment to 0.7±0.2 or 0.9±0.1, respectively. The predicted adult height was increased significantly and progressively during therapy. The levels of serum LH, FSH and E2 returned to the prepubertal condition. No significant side effects of therapy were noted. The most common side effect during SC treatment was that a non-irritating, 1 cm in di- ameter mass was palpated at the site of subcutaneous injection in the abdominal wall of patients, which disappeared after 6- 12 weeks. Two girls had minimal withdrawal vaginal bleeding episodes after the first injection. It was concluded that both IM and SC triptorelin administrations were clinically effective. They induce profound suppression of hypothalamic-pituitary-gonadal axis while stabilizing height velocity, slowing bone maturation and increasing predicted adult height. These results suggest that subcutaneous injection of triptorelin in 6-weeks intervals at a dosage of 3.75 mg be a safe and acceptable regimen for ICPP.

Rare mutation in MKRN3 in two twin sisters with central precocious puberty: Two case reports

BACKGROUND Caused by premature activation of the hypothalamic-pituitary-gonadal axis,there is increasing incidence of central precocious puberty(CPP),especially in girls.Makorin ring finger protein 3(MKRN3),a maternal imprinted gene with a highly conserved sequence,is the most common genetic etiology associated with CPP.Approximately 50 different mutations in MKRN3 have been found in CPP.CASE SUMMARY This case report involves identical twin sisters presenting with premature thelarche at the age of 6 years.The left hand bone age of both patients revealed advanced age(9 years).Pelvic B ultrasound indicated enlargement of the ovaries.Luteinizing hormone(LH)releasing hormone testing confirmed CPP.Wholeexome sequencing detected the c.841C>T mutation in MKRN3,leading to a single base substitution,in the twins.This mutation was inherited from the father and paternal grandmother.After 3 mo of treatment with a gonadotropin-releasing hormone analog,levels of LH,follicle-stimulating hormone,and estradiol in the proband’s sister returned to normal levels.CONCLUSION Here,we report a rare mutation(c.841C>T)in MKRN3 in identical twin sisters with CPP.

Independent Relationship between Body Mass Index and LH Peak Value of GnRH Stimulation Test in ICPP Girls: A Cross-sectional Study

The effect of obesity on idiopathic central precocious puberty（ICPP） girls is still under discussion. The relationship between body mass index（BMI） and sexual hormone levels of gonadotropin-releasing hormone（GnRH） stimulation test in ICPP girls is controversial and the underlying mechanism is unclear. This study aims to further explore the independent effect of excess adiposity on peak luteinizing hormone（LH） level of stimulation test in ICPP girls and the role of other related factors. A retrospective cross-sectional study was performed on 618 girls diagnosed as having ICPP, including 355 cases of normal weight, 99 cases of overweight and 164 cases of obese. The results showed that obese group had more progressed Tanner stage and no significant difference（P=0.28） in LH peak was found as basal LH value was used as a covariate. The obese group had higher total testosterone（TT）, adrenocorticotrophic hormone（ACTH）, 17-α hydroxyprogesterone（17-αOHP） and androstendione（AN）, with significantly increased fasting insulin（FIN） and homeostasis model of assessment for insulin resistance index（HOMA-IR）. Stratified analysis showed inconsistency of the relationship between BMI-standard deviation score（BMI-SDS） and LH peak in different Tanner stages（P for interaction=0.017）. Further smoothing plot showed linear and non-linear relationship between BMI-SDS and LH peak in three Tanner stages. Then linear regression model was used to analyze the relationship between BMI-SDS and LH peak in different Tanner stages, with and without different confounding factors being adjusted. In B2 stage, BMI-SDS was negatively associated with LH peak. In B3 stage, when BMI-SDS 〈1.5, as BMI-SDS increased, the level of LH peak decreased（model Ⅰ： β=–1.8, 95% CI=–4.7 to 1.1, P=0.214）. When BMI-SDS ≥1.5, BMI-SDS was significantly positively associated with LH peak（model Ⅰ： β=4.5, 95% CI=1.7 to 7.4, P=0.002）. In B4 stage, when BMI-SDS 〈1.5, BMI-SDS was negatively associated with LH peak（model Ⅰ： β=–11.6, 95% CI=–22.7 to –0.5, P=0.049）. When BMI-SDS ≥1.5, BMI-SDS was positively associated with LH peak（model Ⅰ： β=–4.2, 95% CI=–3.3 to 11.7, P=0.28）. It is concluded that there is an independent correlation between BMI-SDS and LH peak of stimulation test in ICPP girls, their relationships are different in different Tanner stages, and the effect of BMI-SDS can be affected by adrenal androgens, estradiol and glucose metabolism parameters.

Development and postnatal neurogenesis in the retina: a comparison between altricial and precocial bird species

The visual system is affected by neurodegenerative diseases caused by the degeneration of specific retinal neurons,the leading cause of irreversible blindness in humans.Throughout vertebrate phylogeny,the retina has two kinds of specialized niches of constitutive neurogenesis:the retinal progenitors located in the circumferential marginal zone and Müller glia.The proliferative activity in the retinal progenitors located in the circumferential marginal zone in precocial birds such as the chicken,the commonest bird model used in developmental and regenerative studies,is very low.This region adds only a few retinal cells to the peripheral edge of the retina during several months after hatching,but does not seem to be involved in retinal regeneration.Müller cells in the chicken retina are not proliferative under physiological conditions,but after acute damage some of them undergo a reprogramming event,dedifferentiating into retinal stem cells and generating new retinal neurons.Therefore,regenerative response after injury occurs with low efficiency in the precocial avian retina.In contrast,it has recently been shown that neurogenesis is intense in the retina of altricial birds at hatching.In particular,abundant proliferative activity is detected both in the circumferential marginal zone and in the outer half of the inner nuclear layer.Therefore,stem cell niches are very active in the retina of altricial birds.Although more extensive research is needed to assess the potential of proliferating cells in the adult retina of altricial birds,it emerges as an attractive model for studying different aspects of neurogenesis and neural regeneration in vertebrates.

Precocious puberty: Pathology, related risks, and support strategies

Children are currently starting pubertal development much earlier than 20 to 30 years ago. Data from the National Health and Nutrition Examination Survey (NHANES III) conducted from 1988-1994 revealed that the median age for breast development in white girls was approximately 9.7 years and 8 years in African-American girls versus 10.9 years ago. More recent data, however, indicate that some children are starting pubertal development even earlier (age 7 or 8 in girls or age 9 in boys). Very early pubertal development is identified as precocious puberty, a phenomenon that brings great concern to others besides parents: the child, their peers, school nurses, teachers and counselors. This paper discusses precocious pubertal development, possible causes or relationships, related risks, treatment and helping strategies.

Clinical efficacy of leprerelin acetate with different dosage forms in central precocious puberty girls

Objective:To observe the clinical efficacy of different dosage forms of lepraline acetate(LA)in the treatment of girls with central precocious puberty(CPP).Methods:72 CPP girls treated in the Department of Pediatrics of Huai'an First People's Hospital from February 2021 to August 2022 were included as subjects and divided into two groups:3-month LA group(n=34)and 1-month LA group(n=38).Both group girls were treated for 6 months.Serum hormone levels,body mass index(BMI),bone age/chronological age(BA/CA)and pelvic color ultrasound were detected at 0 and 6 months after treatment,and the changes of various indexes were compared before and after treatment.Results:1)There were no significant differences in baseline data between the two groups before treatment(P>0.05).2)After 6 months of treatment,BA/CA decreased,growth rate slowed down,and predicted adult height increased in both groups(P<0.05),but there were no significant differences between groups(P>0.05).3)After 6 months of treatment,there waere no significant differences in luteinizing hormone(LH)inhibition ratio between the 3 month and 1 month dosage groups(P>0.05).After treatment,the peak value of serum LH and FSH,estradiol level,uterine volume,bilateral ovarian volume,maximum follicle diameter and the number of follicles 4mm were significantly decreased in the two groups,but there were no significant differences between the two groups(P>0.05).4)There were no significant differences in the levels of thyroid hormone,fasting blood glucose and triglyceride between the two groups before and after treatment(P>0.05).Total cholesterol levels were increased after treatment(P<0.05),but there was no significant difference between groups(P>0.05).5)No serious adverse reactions occurred during the treatment of the two dosage forms of LA,but the 3-month dosage form of LA reduced the treatment cost and improved the treatment compliance.Conclusion:The short-term efficacy of 3-month LA in the treatment of CPP in girls is similar to that of 1-month LA.The 3-month dosage form LA is a safe,effective,and economical method for the treatment of CPP in girls.

Patterns of host use by a precocial obligate brood parasite, the Black-headed Duck: ecological and evolutionary considerations

The Black-headed Duck (Heteronetta atricapilla) is unique among obligate avian brood parasites because its highly precocial young leave the host nest shortly after hatching and impose no post-hatching costs on their hosts. Accordingly, we might expect host-parasite interactions in this parasite to differ strikingly from those of other brood parasites — they should be able to parasitize a broad diversity of hosts and be highly successful with these hosts. We conducted the second detailed study ever completed on patterns of host use in Black-headed Ducks. Based on four years of systematic searches of multiple marshes in Argentina, we found no evidence that Black-headed Ducks ever had nests of their own, confirming the previous conclusion that Black-headed Ducks are, indeed, true obligate brood parasites. Contrary to expectation, however, we found that Heteronetta is ecologically dependent on a surprisingly small number of host species — two species of coots and a gull — all of which are widespread and locally abundant species. Other species are numerically less important as hosts either because they are relatively uncommon, or because they are avoided by the ducks. In the three main host species, hatching success of the duck eggs was also surprisingly low (≤ 28%), based on expectations for a precocial parasite, mainly due to host rejection or neglect. Mortality due to predation on host nests, in contrast, was low for all three primary host species. These observations corroborate Weller’s observations from a single-year study. The combination of a dependence on few primary hosts and a relatively low hatching success are inconsistent with some previous hypotheses for the evolution of obligate brood parasitism in Heteronetta. Instead, our observations, and those of Weller, suggest that intense nest predation in Austral wetlands, coupled with an abundance of a few common host species that aggressively defend their nests and obtain high nest success rates, may have been an important factor in the evolution of obligate parasitism in this enigmatic duck.

Investigation of the Cause of Precocious Puberty in an 8-Year-Old Girl Ended up in Juvenile Granulosa and Theca Cell Tumor of the Ovary

Isosexual precocious puberty in girls has several etiologies. Juvenile granulose cell tumor is one of the rarest causes that only stands for 1.5% of ovarian cancers. This tumor mostly encounters in first 2 decades of life. This paper is a report of an 8-year-old girl with precocious puberty that within five months developed breast enlargement followed by menarche. Works which are done to find the underlying cause of precocious puberty revealed juvenile granulosa cell tumor in her left ovary. She then under went laparoscopic surgery and 3 courses of chemotherapy. She did not experience any vaginal bleeding after that and the serum level of estradiol lay among its normal ranges, but after that the tumor relapsed and presented as abdominal pain and a huge mass which under went resection of all afflicted tissues. After 2 courses of chemotherapy, her status deteriorated and unfortunately she died after 6 months from the time of diagnosis. Treatment for this disease is consists of resection surgery and chemotherapy. If this tumor is diagnosed in its early stages, it will be curable, but in its advanced stages, up to 80% of patients die from recurrent tumors. The reported patient was diagnosed at stage IIIC that had poor prognosis.

Application of the assay of urine FSH β-subunit in patients with pubertal disorders

Objective: To evaluate the diagnostic predictive value in the identification of puberty disorders by means of ELISA of β-FSH subunit levels in successively collected urine samples compared to RIA of intact FSH in serum obtained from the normal control subjects and patients with puberty disorders, respectively.Subjects and Methods: Five male and four female volunteers were recruited as controls. Four patients with the hypogonadotropic hypogonadism, five patients with hypergonadotropic hypogonadism, four patients with the central precocious puberty and one patient with isosexual peripheral precocious puberty collected successively their early-morning urine samples for 30 to 32 days.The urine β-FSH subunit was assayed with the method of ELISA, then adjusted by creatinine (Cr) concentration.Results:Comparing with their cotemporary groups, patients with the hypogonadotropic hypogonadism had lower levels of urine β-FSH, and patients with idiopathic hypergonadism had higher levels with irregular fluctuation. Meanwhile, patients with the central precocious puberty had much higher levels of urine β-FSH with irregular peaks, and patients with isosexual peripheral precocious puberty had almost normal levels. The patterns were coincident with the clinical characteristics and serum FSH levels.Conclusion: The ELISA of urine β-FSH subunit possesses a number of advantages over the RIA of serum FSH level, such as low cost, simplicity and reliability in the clinical practice. It can be used for the diagnoses of puberty disorders. In addition, it is possible and much easier, comparing with blood samples, to collect successively urine samples for research of pathophysiological dynamics of FSH secretion in puberty disorders and other reproductive dysfunction.

Precocious In-Vitro Flowering of Perennial Asparagus (Asparagus officinalis L.) Regenerants with a Chemical Inducer

A precocious flowering system of regenerants in asparagus (Asparagus officinalis) was achieved by treatment with a chemical inducer. Somatic embryos withered completely by being processed for 8 - 12 days with 200 μM n-propyl N-(3,4-dichloro-phenyl)carbamate that had been dissolved in distilled water. In contrast, precocious flowering occurred at an extremely low rate (3.4%) when somatic embryos were processed in carbamate dissolved in Murashige and Skoog’s liquid medium. To encapsulate the female and male embryos, we surveyed the optimum conditions of viscosity and concentration of sodium alginate for encapsulating the seeds, and we screened the values of 80 - 120 cps and 2% - 3%, respectively. The synthetic seeds produced also withered when they were processed with the carbamate dissolved in distilled water. However, when Murashige and Skoog’s liquid medium was used for the solvent, the flowering frequency of the synthetic seeds was enhanced (13.3%). Based on our morphological and histological observations, female and male regenerants that were processed with the carbamate solution produced individual flower organs. The conversion of sex expression did not occur. A precocious flowering system would allow a significant reduction in the time required for perennial seedlings to flower and can, therefore, save time required for further experiments that employ floral homeotic mutants.

A Rare Cause of Precocious Puberty and Massive Ovarian Cysts Associated with Hypothyroidism

Van Wyk-Grumbach syndrome (VWGS) is characterized by juvenile hypothyroidism, delayed bone age, isosexual precocious puberty and massive ovarian cysts. We report such a case in a 7-year-old girl who presented with a bilateral pelvic pain, abdominal distension and signs of hypothyroidism. Physical examination showed a breast development and lack of pubic and axillary hair. There was no clitoromegaly. Pelvic ultrasonography and CT scan showed enlarged bilateral multiloculared multicystics ovarian masses. The pituitary MRI was recommended before an elevated prolactin, revealed a large sellar and suprasellar mass. The patient was started on thyroid replacement using L-Thyroxine. Clinically, the patient’s fatigue, pelvic pain, and abdominal distension are resolved. During the follow-up, her thyroid functions and serum prolactin normalized within 8 months. Ultrasonography revealed regression of ovarian cysts in 2 months measuring, with normal sized ovaries in 14 months.

Effects of Nourishing “Yin”-Removing “Fire” Chinese Herb Mixture on the Differential Expression of GABA_AReceptor <i>α</i>Subunits in Hypothalamus of Precocious Puberty Female Rats

GABAergic input to Gonadotropin-releasing hormone (GnRH) neurons is necessary to initiate the onset of puberty and its action mainly depends on GABAA receptor of which the subunit composition, properties and consequently function varies during this period. Nourishing “Yin”-Removing “Fire” Chinese herb mixture, a Chinese herb-based formulation, has been proved that it may retard the initiation of pubertal development in female precocious puberty rats. Our objective is to investigate the effects of Nourishing “Yin”-Removing “Fire” Chinese herb mixture on the expression of GABAA receptor α subunits in hypothalamus. Female Sprague-Dawley rats were divided into normal (N), precocious puberty model (M) induced by danazol, model exposed to saline (MS) and model exposed to Chinese herb mixture (CHM) groups. All rats were administered by the Chinese herb mixture from P15 on. Coefficients of reproductive organs and serum gonadotropins and estradiol levels in M were significantly enhanced while they were significantly decreased in CHM. The hypothalamic GnRH mRNA was also significantly increased in M and in CHM, as well as ERα mRNA. At the mean time, the hypothalamic GABAA receptor α1 and α3 subunits mRNA were more significantly decreased in M than those of N, while they were more significantly enhanced in CHM than those in M (p 0.01), the protein expression of which in hypothalamus had the same trend as the mRNA expression. The evidence suggests that Nourishing “Yin”-Removing “Fire” Chinese herb mixture could significantly retard the sexual development of the precocious rats, and up-regulate the expressions of hypothalamic GABAA receptor α1 and α3 subunits. Our result indicated that GABAA receptor α1 and α3 subunits might involve in the effective treatment of herb mixture on idiopathic precocious puberty.

Unusual Presentation of Precocious Puberty and Alopecia Universalis in Saudi Patients with Autoimmune Polyglandular Syndrome Type 1(APS1) without Any Other Manifestation of the Disease: Case Report and a Brief Review of the Literature

Autoimmune polyglandular syndrome type 1 (APS-1) is one of the rare inherited disorder that affects both sexes alike. Although in specific autoimmune dysfunction associated with this syndrome found to be more common in females than males. It has specific criteria usually presented at a specific age. The object of this clinical case report is to highlight this unusual presentation of such condition which is the presence of APS-1 with precocious puberty and alopecia Universalis without any associated symptoms of APS-1 and the gene variations that never had been found before. And up to our knowledge, this is the 1st case in our population and worldwide that has such combination and this is unusual clinical presentation. Autoimmune polyglandular syndrome type 1 (APS-1) is one of the rare inherited disorder that affects both sexes alike. Although in specific autoimmune dysfunction associated with this syndrome found to be more common in females than males. It has specific criteria usually presented at a specific age. The object of this clinical case report is to highlight this unusual presentation of such condition which is the presence of APS-1 with precocious puberty and alopecia Universalis without any associated symptoms of APS-1 and the gene variations that never had been found before. And up to our knowledge, this is the 1st case in our population and worldwide that has such combination and this is unusual clinical presentation.

Effects of Nourishing “Yin”-Removing “Fire” Chinese Herb Mixture on the Expression of GABAB Receptors in Hypothalamus of Precocious Puberty Female Rats

Objectives: To investigate the potential role of GABAB Receptors (GABABRs) involved in the effect of Nourishing “Yin”-Removing “Fire” Chinese herb mixture (TCM) treatment on precocious puberty. Methods: Female Sprague-Dawley rats were randomly divided into four groups: normal (N), central precocious puberty (CPP) model (M), CPP fed with normal saline (S) and CPP fed with Nourishing “Yin”-Removing “Fire” Chinese herb mixture (TCM). Rats of postnatal day 5 were given a single subcutaneous injection of 240 μg danazol to establish CPP model rats. Rats of S and TCM groups were continuously administered with saline or nourishing “Yin”-removing “Fire” Chinese herb mixture since postnatal day 15. The expression of GABABRs was detected by means of real-time PCR and immunohistochemistry. Results: The expression of hypothalamic GnRH mRNA in M was significantly increased on the day of pre-puberty when compared with that of N (P < 0.01). On the day of onset-puberty, LH levels were higher in M than those in N (P < 0.01), while the serum E2 and LH levels of TCM decreased when compared with those of M (P B1 receptor (GABABR1) immunoreactive cells in the arcuate nucleus (ARN) was decreased in M when compared with that of N (P < 0.05) and increased in TCM compared with that of M (P < 0.05);simultaneously, the expression of GABABR1 mRNA in hypothalamus was significantly decreased in M when compared with that of N (P < 0.01) and increased in TCM compared with that of M (P < 0.01). On the day of onset-puberty, the number of GABABR1 immunoreactive cells in medial septum (MS) was decreased in M compared with that in N (P < 0.05) and increased in TCM comparing with that of M (P < 0.05);meanwhile, the mRNA expression of GABABR1 in hypothalamus was decreased in M compared with that in N (P B2 receptor (GABABR2) immunoreactive cells in the ARN, MS and diagnonal band of broca (DBB) were decreased in M when compared with those of N (P < 0.05) and increased in TCM compared with those of M (P < 0.05) on the day of onset-puberty. At the same time, the mRNA expression of GABABR2 was significantly decreased in M compared with that of N (P < 0.01). Conclusions: These results indicated that the GABABRs might involve in the curative effect of Nourishing “Yin”-Removing “Fire” Chinese herbal mixture on CPP rats.