Development Of Secondary Sexual Characteristics Research Articles

Roles of gonad-inhibiting hormone in the protandric simultaneous hermaphrodite peppermint shrimp†.

To date, the molecular mechanisms of the unique gonadal development mode known as protandric simultaneous hermaphroditism (PSH) are unclear in crustaceans. In this study, cDNA of a gonad-inhibiting hormone (Lv-GIH1) was isolated from the PSH peppermint shrimp Lysmata vittata, and its expression was exclusively found in the eyestalk ganglion. Real-time quantitative polymerase chain reaction (qRT-PCR) revealed that the expression of Lv-GIH1 increased during gonadal development of the functional male stages but decreased significantly at subsequent simultaneous hermaphroditism stage. Further in vitro experiment showed that recombinant GIH1 protein (rGIH1) effectively inhibited Vg expression in the cultured hepatopancreas tissues while the short-term injection of GIH1-dsRNA resulted in reduced expression of Lv-GIH1 and upregulated expression of Vg in the hepatopancreas. Moreover, long-term rGIH1 injection led to significantly reduced expression of Lv-Vg, Lv-VgR, and Lv-CFSH1, subdued growth of oocytes, and feathery setae as a secondary sexual characteristic in females. Interestingly, while germ cells in testicular part were suppressed by rGIH1 injection, the expression of Lv-IAGs showed no significant difference; and long-term GIH1-dsRNA injection results were contrary to those of rGIH1 injection. Taken together, the results of this study indicate that Lv-GIH1 is involved in gonadal development and might also participate in controlling secondary sexual characteristic development in L. vittata by inhibiting Lv-CFSH1 expression.

Diagnosis of Precocious Puberty in Girls

Puberty is one of the most astonishing periods of human life, when significant physical alterations occur along with psychosocial maturation. Precocious Puberty (PP) is defined as the appearance and progressive development of secondary sexual characteristics at a younger age than the general population, i.e. for Caucasian girls before 8 years of age. Untreated precocious puberty usually leads to short stature and can also cause significant emotional and behavioral issues. In recent years, an increased incidence of PP has been found in many countries although several studies now suggest that this trend has slowed down over the last decade in most industrialized countries, while persisting in other countries. Some girls with idiopathic precocious puberty may also have slowly progressive pubertal development without deterioration of their predicted height over a 2-year follow-up period. It is important to determine which girls to treat and the role of the clinician remains crucial. The clinician also needs to be familiar with the terminology of pubertal progression. The aim of this review was to examine the diagnosis of central precocious puberty (CPP) taking in account clinical practice and international literature.

P-06-15 Efficacy of Gonadotropin-Releasing Hormone Agonists in the Clinical Management of Adolescents With Gender Dysphoria: A Prospective Follow-UP Study

Current guidelines recommend the use of gonadotropin-releasing hormone agonists (GnRHas) as the treatment of choice to suppress puberty in adolescents with Gender Incongruence/Gender Dysphoria (GI/GD). The onset of the pubertal physical changes in transgender youth usually leads to a worsening of GD, distress and psychological functioning. GnRHas reduce suffering caused by pubertal development, leaving the body in a neutral state and allowing these adolescents to explore their gender identity. The aim of the present study is to compare psychological functioning before and after GnRHas treatment in a sample of adolescents with GD assessed at the Florence Gender Incongruence Unit and to demonstrate that GnRHas are effective in relieving distress caused by the development of secondary sex characteristics. Fourteen gender dysphoric adolescents were evaluated at 0, 3 and 6 months after the start of GnRHas (triptorelin 3,75 mg every 28 days). The evaluation included physical examination, blood samples and psychometric tests, such as: Youth Self Report (YSR) to measure psychological functioning; Multi-Attitude Suicide Tendency Scale (MAST) to define suicide risk; Beck Depression Inventory (BDI) to evaluate depressive symptoms.

Haemophilia A in a Female Patient with Turner Syndrome

A 28-year-old female presented with occasional swelling of knees and prolonged bleeding after trauma. She also complained of gum bleeding in few occasions. She also gave history of primary amenorrhoea and failure of development of secondary sexual character. There was negative family history of bleeding tendency in both maternal and paternal family. Her investigation profile showed prolonged Partial Thromboplastin Time and reduced factor VIII activity (2.5%). Karyotyping showed (45 XO) Turner syndrome. This is the reported first case of association of Turner syndrome with moderate Haemophilia A in Bangladesh.

SUN-027 Testicular Regression Syndrome, an Underdiagnosed Cause of Hypergonadotropic Hypogonadism

Background: Testicular regression syndrome (TRS), also known as vanishing testes syndrome, is a condition of 46, XY males presenting with male phenotypic genitalia and testicular absence. Normal testes are thought to have once existed in fetal life and subsequently atrophied following a catastrophic event. It may present as partial or complete absence of testicular tissue. Fibrotic remnants are commonly found upon surgical exploration. Case: This is the case of a 20-year-old male with a birth-diagnosis of primary hypogonadism. The patient was born prematurely at 5 months following a motor vehicle accident that resulted in his mother’s death. Neonatal evaluation for cryptorchidism revealed no radiological evidence of intra-abdominal testicular mass. Referral to a pediatric-endocrinologist was done at early childhood. Testosterone replacement was started at 12 years of age and pubarche was adequate. After surgical exploration, a testicular remnant was surgically removed. Pathology report revealed fibrotic tissue, yet no histological testicular tissue was found. Due to lack of testes in the scrotum, testicular prosthesis was implanted at age 14, but the etiology of the hypogonadism was never elucidated. The patient was initially seen in our adult-endocrinology clinics at age 21. Upon evaluation, secondary sex characteristics were adequate for age. Penile length was of 3.5 inches. Bilateral testicular prostheses were palpable, and no gynecomastia was present. Despite testosterone replacement, total testosterone was 3.38 ng/ml (n; 2.41-8.27 ng/ml), FSH was 106 mIU/ml (n; 1.4-18.1 mIU/ml) and LH was 34.7 mIU/ml ml (n; 1.5-9.3 miu/ml). Based on history, laboratory workup and surgical pathology, TRS was presumed as the etiology of this patient’s hypogonadism. Testosterone therapy was adjusted to reach physiological expected levels. Conclusion: TRS is an underdiagnosed cause of hypergonadotropic hypogonadism. It is supposed that the initial embryologic development was normal, followed by a vascular accident. There is no clear recommended approach for evaluating a patient once the diagnosis of TRS is suspected. Diagnostic methods may include hormonal and karyotype testing, imaging, and surgical exploration. Furthermore, although clinical recommendations have been published for other disorders of sex development, TRS management has been understudied. Testosterone replacement therapy at the typical time of puberty ensures the development of secondary sexual characteristics, bone health and pubertal growth. Unlike Klinefelter syndrome and cryptorchidism, TRS has not been associated with increased risk of cancer. Thus, it is important to establish the etiology to avoid invasive and unnecessary workup, which will result in psychological distress and excessive healthcare costs.

Androgen Treatment in Adolescent Males With Hypogonadism.

During adolescence, androgens are responsible for the development of secondary sexual characteristics, pubertal growth, and the anabolic effects on bone and muscle mass. Testosterone is the most abundant testicular androgen, but some effects are mediated by its conversion to the more potent androgen dihydrotestosterone (DHT) or to estradiol. Androgen deficiency, requiring replacement therapy, may occur due to a primary testicular failure or secondary to a hypothalamic–pituitary disorder. A very frequent condition characterized by a late activation of the gonadal axis that may also need androgen treatment is constitutional delay of puberty. Of the several testosterone or DHT formulations commercially available, very few are employed, and none is marketed for its use in adolescents. The most frequently used androgen therapy is based on the intramuscular administration of testosterone enanthate or cypionate every 3 to 4 weeks, with initially low doses. These are progressively increased during several months or years, in order to mimic the physiology of puberty, until adult doses are attained. Scarce experience exists with oral or transdermal formulations. Preparations containing DHT, which are not widely available, are preferred in specific conditions. Oxandrolone, a non-aromatizable drug with higher anabolic than androgenic effects, has been used in adolescents with preserved testosterone production, like Klinefelter syndrome, with positive effects on cardiometabolic health and visual, motor, and psychosocial functions. The usual protocols applied for androgen therapy in boys and adolescents are discussed.

Study on 46 XY Disorders of Sex Development

Introduction: 46 XY disorders of sexual development (DSD) include a wide sphere of phenotypes which can be ambiguous male genitalia with or without hypospadias, unambiguous female genitalia or dysgenetic gonads or any combination of them. Management of these patients depends on the aetiology, age at presentation, gender orientation and advancement in feminization.
 Objectives: To assess the clinical, biochemical, radiological and chromosomal profile of the paediatric patients with suspected DSD attending a tertiary level healthcare centre and plan for appropriate management.
 Materials and Methods: This cross-sectional study was carried out among 30 cases of 46XY DSD attending the paediatric endocrine unit of Bangladesh Institute of Research and Rehabilitation in Diabetes Endocrine and Metabolic Disorders (BIRDEM) General Hospital from May 2016 to April 2017. Clinical, biochemical, radiological and chromosomal evaluations were done to identify the cause of DSD.
 Results: The mean age of the patients recruited in the study was 3.51 (±5.03) years ranging from 13 days old to 13 years old. Among these 30 patients, the chief complaint was ambiguous genitalia in 29 (96.7%) cases, 1 (3.3%) case with Micropenis and 1 (3.3%) case with absence of development of secondary sexual characteristics. The gender of rearing was male in 23 (76.7%) cases and rest as female. Among the patients 5 (16.67%) patients were diagnosed with PAIS, 5 (16.67%) patients with CAIS, 3 (10%) patients had a deficiency of 5αRD and gonadal dysgenesis was found in 5 (16.67%) patients. The corrective surgery was done in 5(16.67%) patients, 16 (53.3%) patients referred to surgeon for operative treatment and 7(23.3%) patients were prescribed to administer testosterone.
 Conclusions: The early presentation, correct identification of the cause and initiation of cause-based treatment can abate the physical and psychosocial complications and may support better gender orientation related adjustability.
 Journal of Armed Forces Medical College Bangladesh Vol.14 (2) 2018: 134-138

Androgens During Infancy, Childhood, and Adolescence: Physiology and Use in Clinical Practice.

We provide an in-depth review of the role of androgens in male maturation and development, from the fetal stage through adolescence into emerging adulthood, and discuss the treatment of disorders of androgen production throughout these time periods. Testosterone, the primary androgen produced by males, has both anabolic and androgenic effects. Androgen exposure induces virilization and anabolic body composition changes during fetal development, influences growth and virilization during infancy, and stimulates development of secondary sexual characteristics, growth acceleration, bone mass accrual, and alterations of body composition during puberty. Disorders of androgen production may be subdivided into hypo- or hypergonadotropic hypogonadism. Hypogonadotropic hypogonadism may be either congenital or acquired (resulting from cranial radiation, trauma, or less common causes). Hypergonadotropic hypogonadism occurs in males with Klinefelter syndrome and may occur in response to pelvic radiation, certain chemotherapeutic agents, and less common causes. These disorders all require testosterone replacement therapy during pubertal maturation and many require lifelong replacement. Androgen (or gonadotropin) therapy is clearly beneficial in those with persistent hypogonadism and self-limited delayed puberty and is now widely used in transgender male adolescents. With more widespread use and newer formulations approved for adults, data from long-term randomized placebo-controlled trials are needed to enable pediatricians to identify the optimal age of initiation, route of administration, and dosing frequency to address the unique needs of their patients.

Insulin-like growth factor 1 is related to the expression of plumage traits in a passerine species

Avian plumage colors and ornaments are excellent models to study the endocrine mechanisms linking sexually selected traits and individual parameters of quality and condition. Insulin-like growth factor 1 (IGF-1) is an evolutionarily highly conserved peptide hormone. Its regulatory role in cell proliferation and differentiation and its high sensitivity to the nutritional state of individuals suggest it as an interesting candidate, possibly providing a link between body condition and individual capacity to grow elaborated ornamental features. We investigated whether IGF-1 levels during molting correlate with the expression of multiple ornaments in a sexually dichromatic passerine species, the bearded reedling (Panurus biarmicus). We collected blood samples of males and females shortly before the molting completed and measured the size and colors of ornamental traits. Our results indicate that in males, structural plumage colors, the size of the melanin-based ornament (beard), and tail length are independent traits. IGF-1 levels are associated with the length of the tail and the expression of male structural plumage components (UV coloration), but not the melanin-based ornament. In females, plumage color and tail length were independent traits, which were not related to IGF-1 levels. To the best of our knowledge, this study provides the first evidence that IGF-1 could play a role in the development of secondary sexual characters in a bird species.Significance statementIGF-1 is an evolutionarily highly conserved peptide hormone, which recently entered the center stage of research enquiry in evolutionary biology. It is considered as one of the key factors shaping individual life histories, but little is known about its effects on sexually selected traits. We investigated whether IGF-1 levels during molting predict the elaboration of multiple ornamental plumage traits in male and female bearded reedlings (Panurus biarmicus). Our results indicate that higher IGF-1 levels had positive effects on male structural plumage colors and tail feather length. This is the first study, bringing indication for a potential role of IGF-1 in the expression of plumage ornaments in a bird species. Our findings suggest that IGF-1 might serve as an ideal candidate to study the mechanisms linking condition and the capacity to develop sexually selected ornaments.

Hypertension, hypokalemia, and left adrenal tumor mimicking primary aldosteronism in a patient with 17α-hydroxylase deficiency

17α-hydroxylase deficiency (17OHD) is a rare disorder of secondary hypertension caused by congenital adrenal hyperplasia. In addition, co-occurrence of an adrenal tumor with 17OHD is extremely rare and easily misdiagnosed. A 33-year-old female with sicca syndrome, persistent hypertension, hypokalemia, and a left adrenal tumor was referred for confirmation of primary aldosteronism. However, the absence of secondary sexual characteristics, persistent growth beyond puberty, and laboratory data of low plasma renin activity, high aldosterone, low cortisol, low sex hormones, elevated adrenocorticotropic hormone, elevated luteinizing hormone, elevated follicle-stimulating hormone, and most importantly, decreased 17-hydroxypregnenolone, supported a diagnosis of 17OHD. We sequenced the CYP17A1 gene of the patient and her parents, which demonstrated genetic defects (D487-S,488-F489 deletion and Y329K418X). 17OHD was diagnosed. The left adrenal tumor was assessed, and a non-functional adrenal incidentaloma was confirmed; NP-59 adrenal cortical scintigraphy and adrenal venous sampling showed no functional activity and non-lateralization. Hormone replacements with estrogen, spironolactone, and prednisolone were given. The patient became more feminized and confident, and her hypertension was controlled. Early diagnosis and treatment of 17OHD not only can prevent delay development of secondary sexual characteristics but also help the patient maintain mental health and improve their quality of life. In addition, the concomitant presence of a left adrenal tumor makes misdiagnosis of a functional adenoma more likely, possibly causing unnecessary surgery and delay inappropriate treatment.

Experience of treatment precocious puberty by gonadotropin-releasing hormone agonists of prolonged action

Central precocious puberty (CPP) occupies an important place in the practice of pediatric endocrinologist. In the treatment of all forms of CPP, there are used drugs of GnRH (gonadotropin-releasing hormone) agonists group, whose pharmacological effect of is based on desensitization of the pituitary gland to the stimulating effect of GnRH. Therapy with agonist of gonadotropin-releasing hormone allows to stop the progression of sexual development, reduce the rate of bone maturation and, thereby, increase the final growth of the child. The article demonstrates the structure of the dispensary group of patients with CPP who were treated with the agonists GnRH of prolonged action. There has been conducted the analysis of the observation results of patients with idiopathic CPP who received 3.75 mg Triptorelin therapy in the standard regimen once every 28 days and transferred to Tryptorelin 11.25 mg once every 3 months, as well as patients with different forms of CPP with a newly established diagnosis. The presented results of treatment with 11.25 mg Triptorelin drugs by intramuscular injection in a regimen of 1 time in 3 months in comparison with the results of treatment with 3.75 mg of Triptorelin patients in the regimen of intramuscular injections once every 28 days in patients with CPP showed their effectiveness. Preparations of the agonists GnRH group of prolonged action inhibit the development of secondary sexual characteristics, lead to a decrease in the size of the internal genitalia in female and external genitalia in male and reduce the progression of bone age. It was also noted that reducing the frequency of injections of drugs of this group from 1 time in 28 days to 1 time in 3 months positively affects the emotional state of children receiving this treatment for a long period (3-6 years).

Dunaliella salina extract alleviates the toxic impact of Dioxin induced endocrine disruption in Nile tilapia

Pollution of lakes and seas in Egypt become a severe problem as it produces a lot of wastes and toxic chemicals. The water pollution induces a lot of endocrine disruptions in aquatic organisms. Several endocrine organs are influencing by pollution such as testes, ovaries, pituitary, hypothalamus, thyroid, and adrenal organs. Propositions of upsetting endocrine chemicals (EDCs) can meddle with fish larval advancement affecting the delicate balance of the biological ecosystem. Endocrine disruption effects on reproductive cycles may affect reproductive behaviour and the development of secondary sexual characteristics. So the main objective of this research is to use marine algae, Dunaliella salina, extract in fish immunity enhancement against pollutants. Nile tilapia fish were exposed to Dioxin (as the main pollutant in the Egyptian environment) after feeding on algae extracts for one month. The results revealed that Dunaliella salina was able to protect the fish against pollution as it enhances the immune capability of Nile tilapia fish due to increase the levels of the antioxidant enzymes and decrease the protein oxidation. Additionally, Dunaliella salina extract was able to decrease the alteration in the expression of genes encoding endocrine hormones such as LH and FSH in the pituitary of Nile tilapia exposed to Dioxin in comparison to control fish. Moreover, the Dunaliella salina extract decreased significantly the DNA damage in brain tissues of Nile tilapia exposed to Dioxin compared with control fish. The results conclude that Dunaliella salina could be used as ameliorative compounds against toxicity of Dioxin.

Central Precocious Puberty Caused by Novel Mutations in the Promoter and 5'-UTR Region of the Imprinted MKRN3 Gene.

Background: Central Precocious Puberty (CPP) is clinically defined by the development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. To date, mutations in the coding region of KISS1, KISS1R, PROKR2, DLK1, and MKRN3 genes have been reported as causative for CPP. This study investigated the presence of causative mutations in both the promoter and the 5′-UTR regions of the MKRN3 gene.Methods: Sanger DNA sequencing was used for screening the proximal promoter and 5′-UTR region of the MKRN3 gene in a group of 73 index girls with CPP. Mutations identified were cloned in luciferase reporter gene vectors and transiently transfected in GN11 cells in order to check for changes in the activity of the MKRN3 promoter. GN11 cells were previously checked for Mkrn3 expression using lentivirus mediated knock-down. In silico analysis was implemented for the detection of changes in the mRNA secondary structure of the mutated MKRN3 5′-UTR.Results: Three novel heterozygous mutations (−166, −865, −886 nt upstream to the transcription start site) located in the proximal promoter region of the MKRN3 gene were identified in six non-related girls with CPP. Four of these girls shared the −865 mutation, one the −166, and another one the −886. A 5′-UTR (+13 nt downstream to the transcription start site) novel mutation was also identified in a girl with similar clinical phenotype. Gene reporter assay evaluated the identified promoter mutations and demonstrated a significant reduction of MKRN3 promoter activity in transfected GN11 cells. In silico analysis for the mutated 5′-UTR predicted a significant change of the mRNA secondary structure. The minimum free energy (MFE) of the mutated 5′-UTR was higher when compared to the corresponding wild-type indicating less stable RNA secondary structure.Conclusion: Our findings demonstrated novel genetic alterations in the promoter and 5′-UTR regulatory regions of the MKRN3 gene. These changes add to another region to check for the etiology of CPP.

Low Frequency of MKRN3 and DLK1 Variants in Chinese Children with Central Precocious Puberty.

Background Central precocious puberty (CPP) is defined by gonadotropin-dependent development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. MKRN3 and DLK1 are two genes, disease-causing variants of which have recently been discovered to cause idiopathic CPP. Methods We screened 173 Chinese patients (9 males and 164 females; 9 familial and 164 sporadic) with ICPP and 43 patients (9 males and 34 females; 3 familial and 40 sporadic) with early puberty for variants in MKRN3. We also screened 19 patients with ICPP and early puberty for variants of DLK1 (17 males and 2 females; 5 familial and 14 sporadic). Results We identified four novel missense variants of MKRN3, c.1138G > A (p.Glu380Lys), c.1420T > A (p.Leu474Met), c.673C > G (p.Leu225Val), and c.1071C > G (p.Ile357Met) in two sporadic cases and three familial cases. According to ACMG standards, two MKRN3 variant (p.Glu380Lys and p.Ile357Met) are likely pathogenic, and two others are of uncertain significance. We also performed bioinformatic analysis to evaluate the impact of variants on MKRN3 protein structures, which showed that Ile357Met locates at the zinc-binding region (C3HC4 RING finger motif), while Glu380Lys is spatially extremely close to the C3HC4 RING finger, MKRN-specific Cys-His domain, and the third C3H1 zinc-finger motif region. Per Glu380Lys, Glu with negative charges has been changed into Lys with positive charges, which may affect the hydrogen bond formation between amino acids and the stability of the local structure, thus affecting the binding of zinc iron to MKRN3 protein. Besides, we did not identify any variants of DLK1 gene in our patients. Conclusions In this study, we report four novel MKRN3 variants in patients with ICPP. Moreover, we did not find any variants of DLK1 gene. Variants of MKRN3 are relatively uncommon in Chinese ICPP patients.

Basal serum luteinizing hormone value as the screening biomarker in female central precocious puberty.

PurposePrecocious puberty refers to the development of secondary sex characteristics before ages 8 and 9 years in girls and boys, respectively. Central precocious puberty (CPP) is caused by premature activation of the hypothalamus-pituitary-gonadal (HPG) axis and causes thelarche in girls before the age of 8. A gonadotropin-releasing hormone (GnRH) stimulation test is the standard diagnostic modality for diagnosing CPP. However, the test cannot always be used for screening because it is expensive and time-consuming. This study aimed to find alternative reliable screening parameters to identify HPG axis activation in girls <8 years old (CPP) and for girls 8–9 years old (early puberty, EP).MethodsFrom January 2013 to June 2015, medical records from 196 girls younger than 9 years old with onset of breast development were reviewed, including 126 girls who had a bone age (BA) 1 year above their chronological age. All patients underwent a GnRH stimulation test, and 117 underwent pelvic sonography. The girls were divided into 4 groups based on age and whether the GnRH stimulation test showed evidence of central puberty. Subanalyses were also conducted within each group based on peak luteinizing hormone (LH) level quartiles.ResultsBasal serum LH level was the most sensitive marker for screening CPP and EP. The cutoff values were 0.245 IU/L for CPP under 8 years old (P=0.049, area under the curve [AUC]=0.764, 88% sensitivity, 48% specificity) and 0.275 IU/L for EP between 8–9 years old (P=0.005, AUC=0.813, 79% sensitivity, 77% specificity). Peak LH level decreased as BMI z-score among subgroups increased when there was no difference in BA; however, higher BA eliminated this effect.ConclusionsBasal serum LH level is a useful screening parameter for diagnosing CPP and EP in girls. Peak LH levels were lower with increasing BMI z-score, although older BA eliminated this effect.

Sex determination and Y chromosome constitutive heterochromatin

In many animals, including us, the genetic sex is determined at fertilization by sex chromosomes. Seemingly, the sex determination (SD) in human and animals is determined by the amount of constitutive heterochromatin on Y chromosome via cell thermoregulation. It is assumed the medulla and cortex tissue cells in the undifferentiated embryonic gonads (UEG) differ in vulnerability to the increase of the intracellular temperature. If the amount of the Y chromosome constitutive heterochromatin is enough for efficient elimination of heat difference between the nucleus and cytoplasm in rapidly growing UEG cells the medulla tissue survives. Otherwise it doomed to degeneration and a cortex tissue will remain in the UEG. Regardless of whether our assumption is true or not, it remains an open question why on Y chromosome there is a large constitutive heterochromatin block? What is its biological meaning? Does it relate to sex determination, sex differentiation and development of secondary sexual characteristics? If so, what is its mechanism: chemical or physical? There is no scientifically sound answer to these questions.

Seasonal variations in serum concentrations of testosterone, testicular volume and neck circumference of fallow deer (Dama dama) kept ex situ in a tropical region.

The fallow deer (Dama dama) is a species of Cervidae commonly kept in captivity, either in commercial farms or in zoos. The reproductive seasonality of this species is well known in the northern hemisphere, where photoperiod is a decisive factor in androgenic activity and, consequently, in the development of secondary sexual characteristics among male adults. The maintenance of this species in tropical regions has been successful, but there are no studies that demonstrate the maintenance of reproductive seasonality under these climatic conditions, which was the objective of the present study. To do so, the present investigation involved 27 fallow deer (D. dama) specimens, of which 14 were adults and 13 prepubescent (<8 months) individuals, all assessed during and outside (December-February) the reproductive season (June-August). The serum concentrations of testosterone, testicular volume, and neck circumference were analyzed among all animals during both seasons. The reproductive season was marked by expressive hormonal concentrations, increasing neck circumference and testicular volume, differing significantly between adults and prepubescent individuals outside the season. Positive correlations were observed among all analyzed variables: mean testicular volume and neck circumference (r = 0.92, p < 0.0001), testicular volume and testosterone concentrations (r = 0.79, p < 0.0001) and between neck circumference and testosterone concentrations (r = 0.67, p < 0.0001). Given the results found, the conclusion is that even under tropical climate conditions the reproductive seasonality of the fallow deer is well defined and may be related to photoperiod.

Obesity and Hypogonadism-A Narrative Review Highlighting the Need for High-Quality Data in Adolescents.

The prevalence of obesity continues to rise in adult and pediatric populations throughout the world. Obesity has a direct impact on all organ systems, including the reproductive system. This review summarizes current knowledge about the effects of obesity on the male reproductive system across age, highlighting the need for more data in children and adolescents. Male hypogonadism is commonly seen in patients with obesity and affects the onset, duration, and progression of puberty. Different pathophysiologic mechanisms include increased peripheral conversion of testosterone to estrone and increased inflammation due to increased fat, both of which lead to suppression of the hypothalamic-pituitary-gonadotropin (HPG) axis and delayed development of secondary sexual characteristics in adolescent males. Evaluation of the HPG axis in obesity includes a thorough history to exclude other causes of hypogonadism and syndromic associations. Evaluation should also include investigating the complications of low testosterone, including increased visceral fat, decreased bone density, cardiovascular disease risk, and impaired mood and cognition, among others. The mainstay of treatment is weight reduction, but medications such as testosterone and clomiphene citrate used in adults, remain scarcely used in adolescents. Male hypogonadism associated with obesity is common and providers who care for adolescents and young adults with obesity should be aware of its impact and management.

SUN-041 Estrogen Pharmacogenetics in Patients with Turner Syndrome

Background: Turner syndrome (TS) is a disorder characterized by complete or partial absence of the second sexual chromosome and the most commonly found abnormalities are short stature and gonadal failure. Most TS patients need estrogen replacement but individual outcomes on uterine volume, breast development and vertebral bone density are highly variable. To our knowledge, the impact of polymorphisms in estrogen receptor 1 (ESR1) over the variability in the development of secondary sexual characteristics and in adult height has not yet been evaluated in TS patients. Objective: To investigate the association among five ESR1 polymorphisms (rs543650, rs1038304, rs2046210, rs2234693 and rs9340799) and breast development, uterine volume, vertebral bone density, FSH and LH levels and adult height in TS patients. Methods: We selected 80 TS patients receiving adult estrogen dose for a minimum period of one year. Patients who had spontaneous complete pubertal development or who have Y chromosome material in karyotype were excluded from analysis. They were submitted to clinical and laboratory evaluation, pelvic ultrasound, bone densitometry and genotyping of the five chosen ESR1 polymorphisms through real time PCR. These polymorphisms were selected through active search in Pubmed and in GWAS catalogs, based on the following criteria: recurrence in studies, being Tag-single nucleotide polymorphisms (Tag-SNPs) or having a minor allele frequency (MAF) which allowed the present study with the available sample. Results: 61% of patients had 45,X karyotype and their mean target height was 158.9cm. 82% of them were treated with rhGH for 5 years on average and they reached a mean adult height of 149cm. Their average age of puberty onset was 14.4 years old and 10% of them had spontaneous thelarche. Their mean uterine volume was 30.1cc but ranged from 5.9 to 83cc. 91% attained adult breast development (Tanner 5) and 93% had normal vertebral bone mass after correction for height (by using the online calculator from University of Washington: courses.washington.edu/bonephys). Only 15% had FSH and/or LH lower than 10 IU/L in two or more measurements. Considering the ESR1 polymorphisms, all of them were in Hardy-Weinberg equilibrium. Statistical analysis with multiple linear regression showed that none of the studied polymorphisms was able to predict any of the above estrogen therapy outcomes in an isolated manner. Conclusion: We could not find a relationship among the studied ESR1 polymorphisms and estrogen therapy outcomes in patients with TS. However, the high variability in estrogen replacement results suggests that genetic variants play an important role. Other efforts to identify polymorphisms associated to estrogen outcomes may allow for individualization of treatment in TS.

Coexistence of Gonadal Dysgenesis and Mullerian Agenesis in a Female with 46 XX Karyotype: A Case Report

Gonadal dysgenesis is a rare genetically heterogeneous disorder characterized by underdeveloped ovaries with consequent, impuberism, primary amenorrhea, and hypergonadotropic hypogonadism. Mullerian agenesis or Mayer‑Rokitansky‑Kuster‑Hauser syndrome is characterized by congenital aplasia of the uterus and the upper part (2/3) of the vagina in a woman with normal development of secondary sexual characteristics and a normal 46 XX karyotype. The association of gonadal dysgenesis and Mayer-Rokitansky-Kuster-Hauser syndrome is very rare and appears to be coincidental. We report a case of a 24-years old woman who presented with primary amenorrhea. The endocrine study revealed hypergonadotrophic hypogonadism. The karyotype was normal, 46,XX. Internal genitalia could not be identified on the pelvic ultrasound and pelvic MRI. There were no other morphological malformations. Keywords: Gonadal dysgenesis; Mayer Rokitansky Kuster Hauser syndrome; Mullerian agenesis; primary amenorrhea; 46,XX.