scholarly journals Possible role of melatonin in precocious and accelerated puberty in females during the COVID-19 pandemic

2021 ◽  
Author(s):  
Stefano Stagi ◽  
Marta Ferrari ◽  
Giada Paiusco ◽  
Maria Moriondo ◽  
Chiara Azzari
Keyword(s):  
Pubertal Development ◽  
Central Precocious Puberty ◽  
Height Velocity ◽  
Healthy Children ◽  
Premature Thelarche ◽  
Complex Process ◽  
Significant Difference ◽  
Salivary Melatonin ◽  
Isolated Premature Thelarche

Abstract BackgroundPubertal development is a complex process influenced by a multitude of factors; among these, the role of melatonin has only been partially investigated. During the COVID-19 pandemic an unexpected increase in cases of precocious and fast puberty was observed.AimsTo evaluate the possible role of salivary melatonin in precocious and accelerated puberty during the COVID-19 lockdown.Patients and MethodsFifty-four females were evaluated from October 2020 to March 2021; of these, 39 children were diagnosed with central precocious puberty (CPP) and 15 with isolated premature thelarche (IPT). Thirty-three healthy children acted as controls. The enrolled patients were asked to take measures the day before the visit to avoid influencing readings of melatonin secretion. Salivary melatonin levels were analyzed using commercially available ELISA kit.ResultsThere was no difference in the time from B2 to diagnosis (months) between IPT and CPP patients. However, the anamnestic and clinical data of our CPP patients confirmed an acceleration in the stages of pubertal development. As expected, subjects with CPP showed a significantly greater stature SDS and height velocity SDS. There were no differences in BMI SDS and Delta BMI SDS. Interestingly, we discovered a significant difference regarding the use of electronic devices between children with CPP, IPT and controls (p < 0.05). Children with CPP showed significantly lower values of salivary melatonin than patients with TPT and controls (p < 0.0001).DiscussionOur results showed a marked reduction in salivary melatonin in children with CPP diagnosed during and after lockdown for COVID-19. Larger studies are needed to confirm and investigate these findings.

The effect of GnRH stimulation on AMH regulation in central precocious puberty and isolated premature thelarche

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Nursel Muratoglu Sahin ◽  
H. Nursun Ozcan ◽  
Aslihan Arasli Yilmaz ◽  
Senay Savas Erdeve ◽  
Semra Cetinkaya ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Pubertal Development ◽  
Follicle Stimulating Hormone ◽  
Central Precocious Puberty ◽  
Complex Interaction ◽  
Breast Development ◽  
Premature Thelarche ◽  
Blood Samples ◽  
Isolated Premature Thelarche ◽  
First Time

Abstract Objectives There is a complex interaction between the anti-müllerian hormone (AMH) and hypothalamic–pituitary–gonadal axis. However, the effect of gonadotropin-releasing hormone (GnRH) stimulation on AMH levels is not clearly known. In the study, we aimed to evaluate the effect of GnRH stimulation on AMH levels in central precocious puberty (CPP) and isolated premature thelarche (PT) groups. Methods Sixty-three girls with breast development before the age of 8 were enrolled in the study. GnRH test was performed on all subjects. Blood samples for follicle-stimulating hormone (FSH), luteinizing hormone (LH), and AMH levels were taken at basal, 40th, and 90th minute of GnRH test. Subjects were grouped as CPP and PT group. Results After GnRH stimulation, AMH levels increased significantly at the 40th minute and the stimulating effect of GnRH on AMH continued till the 90th minute (p: 0.0001). There was a positive correlation between basal and 90th-minute AMH levels (r: 479, p: 0.0001). The highest FSH, LH, and AMH times were significantly different after the GnRH stimulation (p: 0.001, p: 0.001, and p: 0.007). Although the CPP group had a lower basal AMH level than the PT group’s basal AMH level; AMH response to GnRH stimulation was not different (p>0.05). Conclusions In our study, which examined the effect of GnRH stimulation on AMH levels in early pubertal development disorders for the first time, GnRH stimulated AMH secretion rapidly, correlated with basal AMH. Basal AMH levels were lower in patients with CPP than in those with PT; however, the effect of GnRH stimulation on AMH levels was similar in both groups.

scholarly journals Evolutionary Conservation of MKRN3 and Other Makorins and Their Roles in Puberty Initiation and Endocrine Functions

2019 ◽  
Vol 37 (04) ◽  
pp. 166-173 ◽  
Author(s):  
Lydie Naulé ◽  
Ursula B. Kaiser
Keyword(s):  
Wide Spectrum ◽  
Pubertal Timing ◽  
Pubertal Development ◽  
Protein Structures ◽  
Ring Finger ◽  
Central Precocious Puberty ◽  
Evolutionary Conservation ◽  
Loss Of Function ◽  
Underlying Mechanisms

AbstractPuberty is a critical period of development regulated by genetic, nutritional, and environmental factors. The role of makorin ring finger protein 3 (MKRN3) in the regulation of pubertal timing was revealed when loss-of-function mutations were identified in patients with central precocious puberty (CPP). To date, MKRN3 mutations are the most common known genetic cause of CPP. MKRN3 is a member of the makorin family of ubiquitin ligases, together with MKRN1 and MKRN2. The Mkrn genes have been identified in both vertebrates and invertebrates and show high evolutionary conservation of their gene and protein structures. While the existence of Mkrn orthologues in a wide spectrum of species suggests a vital cellular role of the makorins, their role in puberty initiation and endocrine functions is just beginning to be investigated. In this review, we discuss recent studies that have shown the involvement of Mkrn3 and other makorins in the regulation of pubertal development and other endocrine functions, including metabolism and fertility, as well as their underlying mechanisms of action.

scholarly journals Role of Milk-Derived Opioid Peptides and Proline Dipeptidyl Peptidase-4 in Autism Spectrum Disorders

Nutrients ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 87 ◽  
Author(s):  
Beata Jarmołowska ◽  
Marta Bukało ◽  
Ewa Fiedorowicz ◽  
Anna Cieślińska ◽  
Natalia Karolina Kordulewska ◽  
...  
Keyword(s):  
Opioid Peptides ◽  
Mononuclear Cells ◽  
Bovine Milk ◽  
Dipeptidyl Peptidase ◽  
Autism Spectrum ◽  
Control Group ◽  
Healthy Children ◽  
Dipeptidyl Peptidase 4 ◽  
Significant Difference

Opioid peptides released during digestion of dietary proteins such as casein, were suggested to contribute to autism development, leading to the announcement of opioid excess hypothesis of autism. This paper examines role of enzyme proline dipeptidyl peptidase-4 (DPPIV; EC 3.4.14.5) and it is exogenous substrate, β-casomorphin-7 (BCM7) in autism etiology. Our study included measurements of DPPIV and BCM7 concentrations in serum and urine, which were analyzed with ELISA assays and activity of DPPIV was measured by colorimetric test. The effect of opioid peptides from hydrolysed bovine milk on DPPIV gene expression in peripheral blood mononuclear cells (PBMC) in autistic and healthy children was determined using the Real-Time PCR (Polymerase Chain Reaction) method. Our research included 51 healthy children and 86 children diagnosed with autism spectrum disorder (ASD, ICDF84). We determined that the concentration of BCM7 in serum was significantly, 1.6-fold, higher in the ASD group than in controls (p < 0.0001). Concentration of DPPIV was found to also be significantly higher in serum from ASD children compared to the control group (p < 0.01), while we did not notice significant difference in enzymatic activity of serum DPPIV between the two study groups. We confirmed correlation according to the gender between analyzed parameters. The inspiration for this study emanated from clinical experience of the daily diet role in relieving the symptoms of autism. Despite this, we have concluded that milk-derived opioid peptides and DPPIV are potentially factors in determining the pathogenesis of autism; conducted studies are still limited and require further research.

scholarly journals The Peripubertal Decline in Makorin Ring Finger Protein 3 Expression is Independent of Leptin Action

2020 ◽  
Vol 4 (7) ◽  
Author(s):  
Stephanie A Roberts ◽  
Ana Paula Abreu ◽  
Victor M Navarro ◽  
Joy N Liang ◽  
Caroline A Maguire ◽  
...  
Keyword(s):  
Arcuate Nucleus ◽  
Pubertal Development ◽  
Ring Finger ◽  
Central Precocious Puberty ◽  
Mrna Levels ◽  
Ring Finger Protein ◽  
Loss Of Function ◽  
Wild Type ◽  
Finger Protein ◽  
Significant Difference

Abstract A critical body weight is necessary for pubertal development, an effect mediated in part by leptin. The potential regulation by leptin of Makorin Ring Finger Protein 3 (MKRN3), in which loss-of-function mutations are the most common genetic cause of central precocious puberty, has not been previously explored. In mice, expression of Mkrn3 in the hypothalamic arcuate nucleus is high early in life and declines before the onset of puberty. Therefore, we aimed to explore if leptin contributes to the decrease in hypothalamic Mkrn3 mRNA levels observed in mice during pubertal development. We first used a leptin-deficient (ob/ob) mouse model. Mkrn3 mRNA levels in the mediobasal hypothalamus (MBH), which includes the arcuate nucleus, and in the preoptic area (POA), both showed a significant decrease with age from postnatal day (PND) 12 to PND30 in ob/ob mice in both males and females, similar to that observed in wild-type mice. To further explore the effects of leptin on Mkrn3 expression, we exposed prepubertal wild-type mice to high levels of leptin from age PND9-12, which did not result in any significant difference in Mkrn3 expression levels in either the MBH or POA. In summary, regulation of Mkrn3 expression by leptin was not observed in either the MBH or the POA, 2 hypothalamic sites important for pubertal maturation. These data suggest that the decline in Mkrn3 at the onset of puberty may occur independently of leptin and support our hypothesis that MKRN3 is a bona fide controller of puberty initiation.

Effect of GnRHa 3.75 mg subcutaneously every 6 weeks on adult height in girls with idiopathic central precocious puberty

2015 ◽  
Vol 28 (7-8) ◽  
Author(s):  
Yan Liang ◽  
Hong Wei ◽  
Jie Li ◽  
Ling Hou ◽  
Jianling Zhang ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Adult Height ◽  
Recombinant Human Growth Hormone ◽  
Central Precocious Puberty ◽  
Healthy Children ◽  
Idiopathic Central Precocious Puberty ◽  
Significant Difference ◽  
Group A ◽  
Group B ◽  
Age Of Menarche

AbstractTo evaluate the long-term efficacy of triptorelin 3.75 mg subcutaneously every 6 weeks on the final height in girls with idiopathic central precocious puberty (ICPP).Forty females with ICPP received triptorelin 3.75 mg every 6 weeks subcutaneously in our hospital from 2002 to December 2010 and reached their final heights were enrolled. These patients were treated with triptorelin alone (group A, n=17) or triptorelin+recombinant human growth hormone (rhGH) (group B, n=23). Height, weight, annual growth velocity (GV), sexual development, predicted adult height (PAH), and adverse effects were observed. Bone age (BA) and height standard deviation score (SDS) were monitored yearly.Final adult heights (FAHs) were 159.81±1.20 cm and 161.01±1.02 cm in group A vs. group B, which exceeded target height (THt) by 1.51±1.04 cm, 4.86±0.94 cm, respectively. The values of (FAH-THt), (FAH-PAH posttreatment) showed significant difference between the two groups (p<0.05). FAH was positively correlated with Ht SDS-BA at the end of treatment, THt, course of rhGH treatment, and age of menarche (r2=0.66). Body mass index (BMI) increased after treatment in group B. However, there was no significant tendency of increase compared with healthy children at the same age. Ages of menarche and time to menarche from discontinuation were 11.74±0.16 vs. 12.18±0.15 years and 17.41±1.69 vs. 14.71±1.04 months in two groups.The FAH was improved effectively by triptorelin 3.75 mg subcutaneously every 6 weeks, and more height gain could be achieved when rhGH was used concomitantly. BMI maintained steadily and ovarian function restored quickly after treatment discontinuation with the age of menarche similar to that of normal children. Neither significant side effect nor polycystic ovary syndrome was observed.

scholarly journals SUN-097 Gonadotropins Levels Measurement in First Morning Voided Urine as a Diagnostic Tool for Central Precocious Puberty

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Wasawee Sakdinun ◽  
Oranut Komkhum ◽  
Voraluck Phatarakijnirund ◽  
Phairuch Chaiyakul ◽  
Nawaporn Numbenjapon
Keyword(s):  
Precocious Puberty ◽  
Gnrh Agonist ◽  
Central Precocious Puberty ◽  
Height Velocity ◽  
Close Monitoring ◽  
Operating Characteristics ◽  
Premature Thelarche ◽  
Cutoff Value ◽  
Basal Serum ◽  
Serum Lh

Abstract Background: GnRH stimulation test is the gold standard for the diagnosis of central precocious puberty (CPP). However, it is invasive and costly. Previous studies showed that increased urinary gonadotropins (Gn) level in first morning voided (FMV) urine reflected the integration of elevated nocturnal Gn secretions. Therefore, it could be used to diagnose CPP. Nevertheless, its cutoff value for diagnosis of CPP is limited. Objective: To determine the association of Gn levels in FMV urine and serum during pubertal development and establish cutoff value of FMV urinary Gn as an alternative noninvasive method for diagnosis of CPP in girls. Methods: Sixty-one girls who had breast development before 8 years of age with sign of rapid pubertal progression (advanced bone age and/or increased height velocity) underwent subcutaneous GnRH agonist test. FMV urinary Gn were also collected on the same day. Both serum and urinary Gn levels were measured using electrochemiluminescence immunoassay (ECLIA) technique. The definite diagnosis of CPP is based on stimulated serum LH &gt; 5 IU/L. FMV urinary Gn were compared between CPP and premature thelarche (PT) groups. The correlation between serum and urinary Gn were assessed and the cutoff value of urinary Gn to diagnose CPP was established. FMV urinary Gn of 480 Thai school girls (control) were also collected to determine the reference values according to their breast Tanner (BT) stages. Results: FMV ULH level in girls with CPP was significantly higher than that of PT (2.46 VS 0.8 IU/L; median, P &lt;0.001). However, the level of ULH in PT group was not different from control group with BT1. FMV ULH and ULH: UFSH were well correlated with basal serum LH (r=0.63 and 0.73, respectively, Ps&lt;0.001) and peak serum LH (r=0.44 and 0.54, respectively, Ps&lt;0.001). Base on receiver operating characteristics analysis, basal serum LH was the best parameter to differentiate CPP from PT (area under the curve 0.797–0.926). ULH levels at ≥ 1.13 IU/L and ≥ 1.52 provide optimal sensitivity (72.3 and 68.1 %, respectively) and specificity (85.7 and 100 %, respectively). Combined ULH level ≥ 1.13 IU/L with ULH: UFSH ≥ 0.17 increased specificity from 85.7 to 92.9 % for predicting a positive GnRH agonist test. (peak LH ≥ 5 IU/L) Conclusions: First morning voided urinary Gn levels measurement is a highly potential method for the diagnosis of CPP in girls due to its good correlation with GnRH agonist test. Further study in a larger number of patients with close monitoring of clinical outcome is required before recommending as a standard investigation in CPP.

Thelarche variant: A new syndrome of precocious sexual maturation?

1990 ◽  
Vol 123 (5) ◽  
pp. 481-486 ◽  
Author(s):  
Richard Stanhope ◽  
Charles C. D. Brook
Keyword(s):  
Precocious Puberty ◽  
Sexual Maturation ◽  
Central Precocious Puberty ◽  
Clinical Findings ◽  
Breast Development ◽  
Gnrh Analogue ◽  
Gonadotropin Secretion ◽  
Premature Thelarche ◽  
Isolated Premature Thelarche ◽  
Depot Injections

Abstract. We describe 10 girls (mean age 3.7 years, range 1.9-6.9) with precocious sexual maturation and clinical findings intermediate between those of premature thelarche and central precocious puberty. Studies of spontaneous gonadotropin secretion and ovarian ultrasound morphology also revealed findings intermediate between those of isolated premature thelarche and central precocious puberty. There was no response in 6 of the girls treated with GnRH analogue, whether administered intranasally, sc, or by monthly depot injections. We have called this condition thelarche variant because the gonadotropin independence and cyclical nature of breast development may well be due to a lesion of folliculogenesis.

scholarly journals Precocious puberty: a clinical review

2018 ◽  
Vol 7 (3) ◽  
pp. 771
Author(s):  
Pallavee P. ◽  
Rupal Samal
Keyword(s):  
Precocious Puberty ◽  
Pubertal Development ◽  
Psychosocial Problems ◽  
Central Precocious Puberty ◽  
Biochemical Tests ◽  
Gnrh Analogues ◽  
Premature Thelarche ◽  
Epiphyseal Fusion ◽  
Peripheral Precocious Puberty

Precocious puberty is defined as pubertal development occurring more than 2.5 standard deviations earlier than the average age. It may comprise of central or gonadotropin-dependent precocious puberty and peripheral or gonadotropin-independent precocious puberty. Variants of precocious puberty include premature thelarche, premature pubarche and isolated premature menarche which principally implies onset of menstruation without any other signs of sexual development. Precocious puberty may have long-term consequences including short stature later on in adulthood owing to premature epiphyseal fusion as also psychosocial problems. Evaluation includes a detailed history, physical examination, biochemical tests and imaging directed towards detecting the cause. Gonadotropin Releasing Hormone (GnRH) analogues are effective for treatment of central precocious puberty. Treatment of peripheral precocious puberty should be based on the cause. Isolated variants are usually normal but should be closely monitored. Multi-speciality consultation with involvement of pediatricians and enocrinologists may improve treatment outcomes in these children, who otherwise pose significant challenges to the gynaecologist.

scholarly journals The Role of Pediatric Nutrition as a Modifiable Risk Factor for Precocious Puberty

Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1353
Author(s):  
Valeria Calcaterra ◽  
Elvira Verduci ◽  
Vittoria Carlotta Magenes ◽  
Martina Chiara Pascuzzi ◽  
Virginia Rossi ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Pubertal Development ◽  
Protective Role ◽  
Positive Influence ◽  
Early Puberty ◽  
Future Health ◽  
Childhood Nutrition ◽  
Nutritional Recommendations ◽  
Complex Process

Puberty is a critical phase of growth and development characterized by a complex process regulated by the neuroendocrine system. Precocious puberty (PP) is defined as the appearance of physical and hormonal signs of pubertal development at an earlier age than is considered normal. The timing of puberty has important public health, clinical, and social implications. In fact, it is crucial in psychological and physical development and can impact future health. Nutritional status is considered as one of the most important factors modulating pubertal development. This narrative review presents an overview on the role of nutritional factors as determinants of the timing of sexual maturation, focusing on early-life and childhood nutrition. As reported, breast milk seems to have an important protective role against early puberty onset, mainly due to its positive influence on infant growth rate and childhood overweight prevention. The energy imbalance, macro/micronutrient food content, and dietary patterns may modulate the premature activation of the hypothalamic–pituitary–gonadal axis, inducing precocious activation of puberty. An increase in knowledge on the mechanism whereby nutrients may influence puberty will be useful in providing adequate nutritional recommendations to prevent PP and related complications.

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