Gonadotropin releasing hormone analogue treatment of central precocious puberty is not associated with altered prevalence of polycystic ovary syndrome: a single center cohort study

Background There is conflicting evidence regarding an association between gonadotropin releasing hormone analogue (GnRHa) therapy and polycystic ovary syndrome (PCOS). This study aimed to compare the prevalence of endocrine disorders, primarily PCOS, between women who had been treated with GnRHa for central precocious puberty (CPP) and those who were not treated. Methods This was a retrospective cohort study, including women diagnosed with central precocious puberty between 1989 and 2011 in a university affiliated tertiary medical center. Data collected included demographic data, medical background, clinical presentation at diagnosis and duration of treatment (zero for non-treated). Gynecologic and endocrine long-term outcomes were compared by treatment group. Results Fifty-one women were included in the study, 27/51 had been treated with gonadotropin releasing hormone analogue (GnRHa). Overall prevalence of PCOS was 19.6%. No statistically significant difference in prevalence of PCOS was demonstrated between the treated and non-treated groups. Similarly, overall prevalence of either clinical or laboratory hyper-androgenism, was 29.4% and 33.3%, for the treatment and non-treatment groups respectively (p = non-significant). Conclusions GnRHa treatment for precocious puberty is not associated with increased risk of polycystic ovary syndrome.

Efficacy of poly (lactic-co-glycolic acid) microparticles as a gonadotropin-releasing hormone analogue delivery system to stimulate ovulation of peled Coregonus peled

The aim of the study was to determine the efficacy of poly (lactic-co-glycolic acid) microparticles as a carrier of gonadotropin-releasing hormone analogues (GnRHa) for induction of ovulation in peled Coregonus peled. Female peled were injected intraperitoneally with 1) saline solution only (control), 2) mammalian GnRHa at 25 µg/kg body weight, 3) GnRHa in 753-type microparticles at 50 µg/kg, or 4) GnRHa in 653-type microparticles at 50 µg/kg. Blood plasma samples were taken on days 0, 4, 8, and 12 post-injection. All hormone treatments induced synchronous ovulation and higher cumulative ovulation compared to controls. Hormone treatments did not affect relative fecundity or the percentage of eyed eggs. Testosterone level decreased toward the onset of ovulation. On day eight of the trial, the testosterone level was significantly lower in hormone-treated groups compared to the control group. The level of 17β-oestradiol showed a decreasing trend post-injection, with the lowest observed level on day eight. Our results demonstrate that ovulation can be induced in the peled by the sustained – release of GnRHa in poly (lactic-co-glycolic acid) microparticles, but the treatment does not improve reproductive performance.

Artificial propagation and embryonic growth in Stinging catfish, Heteropneustes fossilis (Bloch, 1794) using S-GnRHa (salmon gonadotropin releasing hormone analogue)

An experiment was performed to observe the potentiality of synthetic hormone analogue in artificial propagation i.e., the embryonic and larval development of Heteropneustes fossilis. Broodfish were injected with S-GnRHa according to the following concentration: 1, 2.5 and 5 ml kg-1 of body weight (BW) to females and 0.5, 1.125 and 2.5 ml kg-1 BW to males, in treatment groups T1, T2 and T3, respectively each with three replicates. The fishes were ovulated at about 10-11 hours after the hormone injection. Result showed the highest fertilization (83.11±1.36) and hatching rate (89.56±1.04) in T2, whereas ovulation rate was 100% in all treatment groups. First cleavage was observed in 30 minutes of post-fertilization. Embryonic developmental period sequentially for 2-cell, 4-cell, 8-cell, 16-cell, 32-cell, 64-cell, Morula, Blastula, Gastrula, somatic formation, yolk-plug, twisting movement and pre-hatching were 00:30, 00:45, 01:10, 01:30, 02:00, 02:30, 03:00, 04:00, 06:40, 09:00-18:00, 19:00, 20:00-21:00 and 22:00 hours, respectively. Hatching occurred after 23:00 hours of fertilization. Finally, the current result suggested that S-GnRHa might be an effective synthetic hormone in artificial propagation of H. fossilis.

Evaluation of the Binding Affinity of a Gonadotropin-Releasing Hormone Analogue (GnRH-a) Buserelin through In Silico and In Vivo testing in Clarias magur

Aim: To evaluate the binding affinity and biological potency of gonadotropin releasing hormone analogue (GnRHa) Buserelin (‎C60H86N16O13) based on in silico and in vivo testing for induced breeding in Clarias magur. Background: Many attempts have been made to induce C. magur but encouraging results have not yet been achieved. Hence, it is the need of the hour to find out more potent analogues or other bio-molecules for induced breeding in C. magur to facilitate sustainable aquaculture. Objective: To determine the binding affinity of C. magur GnRH receptor through in silico and its validation for induced breeding of C. magur. Methods: Buserelin (‎C60H86N16O13) was selected as the potential GnRHa after screening several peptides for their binding energy with the C. magur GnRH receptor. The induced breeding trial was set up at ICAR-CIFE Powarkheda Centre, M.P. India, and Buserelin was administered in different doses to the brooders along with the dopamine inhibitor domperidone. The standard treatment with the commercial salmon GnRH (sGnRH) analogue Ovaprim® (Syndel, USA) was used as the control. Results: The 3-D structure of C. magur GnRH receptor was generated using MODELLER software. Molecular docking studies revealed the binding preference of the receptor as chicken (c) GnRH-II > Buserelin > sGnRH > catfish (cf) GnRH > human (m) GnRH. Though Buserelin showed better binding affinity compared to sGnRH, induced breeding experiments with magur showed similar performance of the ligands at the equivalent dose of 20 µg/kg B.W., but the spontaneous release of milt from the males was not obsereved in both the cases. Significantly better reproductive parameters were recorded with Buserelin at the dose of 30 µg/kg B.W. Conclusion: The study revealed that that the GnRHa Buserelin can be used as an effective inducing agent for breeding in C. magur.

Short-term effects of gonadotropin-releasing hormone analogue treatment on leptin, ghrelin and peptide YY in girls with central precocious puberty

Objectives To determine appetite-regulating hormone levels in girls with central precocious puberty (CPP) before and after 20 weeks of gonadotropin-releasing hormone analogue (GnRH-A) treatment. Methods Eighteen newly diagnosed CPP girls were enrolled. Body composition measured by bioelectrical impedance analysis and GnRH-A test were performed with fasting serum leptin, ghrelin and peptide YY (PYY) measurements at baseline (before) and after 20 weeks of GnRH-A treatment. Results Following GnRH-A treatment, all patients had prepubertal gonadotropin and estradiol levels. Mean (SD) fat mass index (FMI) was significantly increased from 4.5 (1.7) to 5.0 (1.8) kg/m2 after treatment. Also, median (IQR) serum leptin level was significantly increased from 6.9 (4.2–8.6) to 7.4 (5.3–13.1) ng/mL. FMI had a positive correlation with serum leptin level (r=0.64, p=0.004). In contrast, no significant changes of serum ghrelin and PYY levels were observed. Conclusions Decreased estrogen following short-term GnRH-A treatment in CPP girls may cause an increase in appetite and consequently an elevation of FMI. Increased serum leptin may be a result of having increased FMI secondary to an increase in appetite.

Gonadotropin releasing hormone analogue therapy in girls with idiopathic precocious puberty/early-fast puberty: dynamics in adiposity indices, eating habits and quality of life

Background The impact of gonadotropin-releasing-hormone-analogue (GnRHa) treatment on weight and body composition is controversial. Exploring the nutritional, psychological patterns of this population may aid to clarify this propensity to gain weight. This prospective observational study aimed to evaluate longitudinal changes in adiposity, nutrition and quality of life in girls with central precocious/early-fast puberty (CPP/EFP) during GnRHa treatment. Methods Thirty-two GnRHa-treated girls with CPP/EFP and 27 prepubertal girls (7–10 years) were included in the analysis. Outcome measures assessed at baseline for CPP/EFP and the control groups and during up to two years of GnRHa treatment for the CPP/EFP group, included anthropometrics, body-composition, basal-metabolic-rate (BMR), 3-day food-diaries, child eating-behavior questionnaire, and pediatric quality-of-life questionnaire (PedsQL). Results Girls with CPP/EFP had higher pretreatment BMI-SDS, fat percentages, waist circumference and waist-per-height (p<0.01 for all), and lower psychosocial functioning than controls (p<0.05). Changes in anthropometric and body composition measurements indicated a gradual increase in adiposity and a decrease in muscle mass (p<0.001 for all). Dynamics in body composition could not be explained by the participants’ self-reported dietary patterns and physical activity levels or by the measured BMR, which revealed an adequate and relatively low energy intake as compared to energy requirements. A gradual decline in physical functioning (PedsQL) after one and two years of GnRHa treatment was observed (p<0.001). Conclusions Our findings highlight the need for comprehensive surveillance in girls with CPP/EFP. Dynamics in weight status and body composition during GnRHa treatment indicate the need for tailored nutritional and physical activity counseling aimed at preventing obesity.

Advancement in spawning period of Labeo dyocheilus (McClelland, 1839) in the mid Himalayan regions by hormonal manipulation using Ovatide

An attempt was made to advance the spawning period of Labeo dyocheilus (McClelland, 1839) by pretreatment with the synthetic gonadotropin releasing hormone analogue, Ovatide. Total 12 females and 24 males (1: 2 ratio) were used for breeding operations conducted during 30th May to 30th June 2016 comprising six sets. Female fishes of set I to IV were pretreated with intramuscular injection of the ovatide at the rate 0.3 ml kg-1 body weight twice at an interval of two weeks while males were injected @ 0.1 ml kg-1 body weight once before 15 days of induced breeding trial for achieving advance maturity and spawning during pre-spawning phase. Fishes of set V and VI were not subjected to any pretreatment with ovatide. On 30th of June all the six breeding sets were were treated with ovatide for induced spawning. Female and males were injected at 0.7 ml kg-1 and 0.3 ml kg-1 of body weight, respectively and left overnight in FRP tanks for spawning. Results indicated that in sets I to IV, fishes successfully spawned and fertilised eggs were collected in morning hours whereas fishes of set V and VI failed to spawn. Fertilisation and survival rates recorded were 79-82% and 67-71%, respectively. Results indicated that treatment of ovatide during prespawning phase is beneficial for advancing the gonadal maturity, successful induced spawning and prolonging the breeding period which may play a key role in production of substantial quantity of seed of L. dyocheilus.