Puberty is a pivotal biological process that completes sexual maturation to achieve full reproductive capability. It is a major transformational period of life, whose timing is strongly affected by genetic makeup of the individual, along with various internal and external factors. Although the exact mechanism for initiation of the cascade of molecular events that culminate in puberty is not yet known, the process of pubertal onset involves interaction of numerous complex signaling pathways of hypothalamo-pituitary-testicular (HPT) axis. We developed a classification of the mechanisms involved in male puberty that allowed placing many genes into physiological context. These include (i) hypothalamic development during embryogenesis, (ii) synaptogenesis where gonadotropin releasing hormone (GnRH) neurons form neuronal connections with suprahypothalamic neurons, (iii) maintenance of neuron homeostasis, (iv) regulation of synthesis and secretion of GnRH, (v) appropriate receptors/proteins on neurons governing GnRH production and release, (vi) signaling molecules activated by the receptors, (vii) the synthesis and release of GnRH, (viii) the production and release of gonadotropins, (ix) testicular development, (x) synthesis and release of steroid hormones from testes, and (xi)the action of steroid hormones in downstream effector tissues. Defects in components of this system during embryonic development, childhood/adolescence, or adulthood may disrupt/nullify puberty, leading to long-term male infertility and/or hypogonadism. This review provides a list of 598 genes involved in the development of HPT axis and classified according to this schema. Furthermore, this review identifies a subset of 75 genes for which genetic mutations are reported to delay or disrupt male puberty.
Adolescent ; Male ; Humans ; Adult ; Child ; Gonadotropin-Releasing Hormone ; Gonadotropins/metabolism* ; Hypogonadism ; Testis/metabolism* ; Puberty/physiology* ; Sexual Maturation

Endometrial polyps are localized outgrowths of glands and stroma within the endometrium primarily caused by hyperestrogenism. They are common causes of abnormal uterine bleeding and infertility by altering the endometrial surface. Polyps may be small, large (measuring more than one centimeter), or giant (more than 4 centimeters in size). Large and giant polyps are very rare and prone to oncologic malformation, thus biopsy is recommended. Endometrial resection with biopsy is the gold standard of treatment, but could be difficult since giant endometrial polyps occupy the entire endometrial cavity resulting to morbidity and failure on hysteroscopy. Limited case reports and studies have used gonadotropin releasing hormone (GnRH) agonist as preoperative therapy to decrease polyp size prior to hysteroscopic resection. The aim of this case report is to discuss a rare case of giant endometrial polyp treated with neoadjuvant GnRH agonist prior to hysteroscopic resection, and to present the recent literature regarding giant endometrial polyps.

OBJECTIVE: To elucidate the association between clinical and laboratory characteristics and pituitary magnetic resonance imaging (MRI) abnormalities in young female patients with hypogonadotropic hypogonadism (HH). METHODS: We retrospectively investigated a series of 74 female patients (age range, 14–42 years) with normoprolactinemic HH who underwent pituitary MRI. Pubertal milestones and hormonal features of patients with small pituitary glands (PGs) and space-occupying lesions were compared with those of patients with normal PGs. RESULTS: The overall frequency of abnormal PGs was 35.1%, with space-occupying lesions observed in 8 patients (10.8%), and small PG observed in 18 patients (24.3%). The mean serum gonadotropin level was not different between patients with and without pituitary MRI abnormalities (P>0.05). Space-occupying lesions were not associated with low gonadotropin levels, type of amenorrhea, or presence of secondary sex characteristics. The frequency of space-occupying lesions was higher in patients with interrupted puberty (25.0%) than in patients who did not go through puberty (4.8%) or had a normal puberty (9.8%), but were not statistically significant (P>0.05). Small PG was associated with low gonadotropin levels and type of amenorrhea (P<0.05). CONCLUSION: Clinically significant space-occupying lesions were not associated with low gonadotropin levels, type of amenorrhea, or presence of secondary sex characteristics. However, the frequency of space-occupying lesions was higher in patients with interrupted puberty than in patients who did not go through puberty or who with normal puberty.
Adolescent ; Amenorrhea ; Female ; Gonadotropins ; Humans ; Hypogonadism ; Magnetic Resonance Imaging ; Pituitary Gland ; Puberty ; Puberty, Delayed ; Retrospective Studies ; Sex Characteristics

BACKGROUND: Provision of optimal endometrial stromal cells is essential in uterine tissue engineering. Culture of these cells is significantly influenced by gonadotropin hormones. This investigation attempted to define the proliferation profiles of murine uterine endometrial stromal cells during in vitro culture with recombinant follicle stimulating hormone (rFSH), urinary follicle stimulating hormone (uFSH), and human chorionic gonadotropin (hCG). METHODS: Murine uterine endometrial stromal cells were collected from 8-week-old mice and cultured in vitro up to 72 h, with rFSH, uFSH, or hCG. Cell cycles were analyzed by BrdU assay, and cyclin D1 expression was evaluated according to dose and duration of gonadotropin treatment. RESULTS: BrdU assay showed a further inhibitory effect on murine uterine endometrial stromal cell proliferation when cultured with rFSH compared to uFSH, and a similar inhibitory proliferation profile when cultured with hCG at a specific range of concentrations. The expression of cyclin D1 of murine uterine endometrial stromal cells was down-regulated when cultured with rFSH, uFSH, or hCG, compared to control. CONCLUSIONS: FSH may inhibit the proliferation of murine uterine endometrial stromal cells during in vitro culture. rFSH may have more significant inhibitory effects on the proliferation of endometrial stromal cells than uFSH. Establishing an optimal endocrine milieu is necessary using more advanced combination of female hormones for in vitro culture of this type of cells.
Animals ; Bromodeoxyuridine ; Cell Cycle ; Chorionic Gonadotropin ; Cyclin D1 ; Female ; Follicle Stimulating Hormone ; Gonadotropins ; Humans ; In Vitro Techniques ; Mice ; Stromal Cells ; Tissue Engineering ; Uterus

PURPOSE: The aim of this study was to investigate how type I diabetes mellitus (T1D) affects the folliculogenesis and oocyte development, fertilization, and embryo development. MATERIALS AND METHODS: A comparative animal study was conducted using two different mouse models of T1D, a genetic AKITA model and a streptozotocin-induced diabetes model. Ovarian function was assessed by gross observation, immunoblot, immunohistochemistry, oocyte counting, and ELISA for serum hormones (insulin, anti-Mullerian hormone, estradiol, testosterone, and progesterone). Maturation and developmental competence of metaphase II oocytes from control and T1D animals was evaluated by immunofluorescent and immunohistochemical detection of biomarkers and in vitro fertilization. RESULTS: Animals from both T1D models showed increased blood glucose levels, while only streptozotocin (STZ)-injected mice showed reduced body weight. Folliculogenesis, oogenesis, and preimplantation embryogenesis were impaired in both T1D mouse models. Interestingly, exogenous streptozotocin injection to induce T1D led to marked decreases in ovary size, expression of luteinizing hormone/chorionic gonadotropin receptor in the ovaries, the number of corpora lutea per ovary, oocyte maturation, and serum progesterone levels. Both T1D models exhibited significantly reduced pre-implantation embryo quality compared with controls. There was no significant difference in embryo quality between STZ-injected and AKITA diabetic mice. CONCLUSION: These results suggest that T1D affects folliculogenesis, oogenesis, and embryo development in mice. However, the physiological mechanisms underlying the observed reproductive effects of diabetes need to be further investigated.
Animals ; Anti-Mullerian Hormone ; Biomarkers ; Blood Glucose ; Body Weight ; Corpus Luteum ; Diabetes Mellitus ; Diabetes Mellitus, Type 1 ; Embryonic Development ; Embryonic Structures ; Enzyme-Linked Immunosorbent Assay ; Estradiol ; Female ; Female ; Fertility ; Fertilization ; Fertilization in Vitro ; Gonadotropins ; Humans ; Immunohistochemistry ; Lutein ; Mental Competency ; Metaphase ; Mice ; Oocytes ; Oogenesis ; Ovary ; Pregnancy ; Progesterone ; Reproduction ; Streptozocin ; Testosterone

BACKGROUND: Follicle-stimulating hormone (FSH), a gonadotropin secreted by the pituitary gland, is a representative secondary sex hormone and an important indicator of reproductive function. The effects of heavy metals such as lead, cadmium, and mercury on humans have been studied, but reports on their effects on sex hormone levels are lacking. Therefore, we investigated the relationship between heavy metal exposure and FSH levels in Korean men and postmenopausal women. METHODS: A total of 4,689 adults (2,763 men and 1,926 postmenopausal women aged 50 years or over) who participated in the Second Korean National Environmental Health Survey (2012–2014) were included. We compared differences in serum FSH levels by demographic characteristics using the t-test and analysis of variance. Multiple linear regression analysis was used to determine the relationship between the blood levels of lead and mercury and the urine cadmium level, and serum FSH levels. RESULTS: On multiple linear regression analysis, lead exposure was positively associated with serum FSH concentrations in postmenopausal women (β = 2.929, p = 0.019). However, we found no significant association between serum FSH concentration and blood lead and mercury levels, or urine cadmium level, in men. CONCLUSIONS: This study suggests that lead exposure can affect the FSH level in postmenopausal women. Further studies are needed to evaluate the effects of low-dose long-term exposure to heavy metals on sex hormones.
Adult ; Cadmium ; Environmental Health ; Female ; Follicle Stimulating Hormone ; Gonadal Steroid Hormones ; Gonadotropins ; Humans ; Linear Models ; Male ; Metals, Heavy ; Pituitary Gland

Mutations in the CHD7 gene, encoding for the chromodomain helicase DNA-binding protein 7, are found in approximately 60% of individuals with CHARGE syndrome (coloboma, heart defects, choanal atresia, retarded growth and development, genital hypoplasia, ear abnormalities and/or hearing loss). Herein, we present a clinical case of a 14-year-old male presenting for evaluation of poor growth and pubertal delay highlighting the diagnostic challenges of CHARGE syndrome. The patient was born full term and underwent surgery at 5 days of life for bilateral choanal atresia. Developmental milestones were normally achieved. At age 14 his height and weight were
Adolescent ; CHARGE Syndrome ; Choanal Atresia ; Diagnosis ; Ear ; Follicle Stimulating Hormone ; Follow-Up Studies ; Genetic Testing ; Gonadotropins ; Growth and Development ; Hearing ; Heart ; Humans ; Luteinizing Hormone ; Male ; Olfaction Disorders ; Puberty, Delayed ; Testis ; Testosterone

PURPOSE: The standard method used to diagnose central precocious puberty (CPP) is the gonadotropin releasing hormone stimulation test (GnRHST). However, this test is inconvenient for children because it is time-consuming and requires multiple samples. This study aimed to determine the reliability of morning unstimulated luteinizing hormone (mLH) level when screening for CPP, with an emphasis on the influence of diurnal variation. METHODS: This study included 160 girls with signs of early puberty (SMR 2) under 8 years of age. They were classified as CPP or non-CPP based on their standard GnRHST. The auxological, biochemical, and hormonal characteristics of subjects were retrospectively evaluated. The prognostic value of single morning unstimulated gonadotropin level was examined for use in CPP screening. RESULTS: Of 160 patients, 121 (75.6%) presented with CPP, and 39 (24.4%) were determined to be prepubertal. The mLH/mFSH (morning unstimulated follicular stimulating hormone) ratio showed significant differences between the 2 groups (P<0.001). The mLH was correlated with GnRHST variables (r=0.532, P<0.001). The mLH cutoff point when screening for CPP was 0.22 IU/L, which had sensitivity and specificity of 69.4% and 82.1%, respectively. In regression analysis, bone age (BA) (odds ratio [OR], 1.018; 95% confidence interval [CI], 0.967–1.071; P=0.506) and body mass index (BMI) (OR, 0.874; 95% CI, 0.583–1.310; P=0.515) were not significant predictors. The mLH≥0.22 IU/L group (OR, 9.596; 95% CI, 3.853–23.900; P<0.001) was highly suggestive of CPP. CONCLUSIONS: In this study, single morning unstimulated luteinizing hormone had clinical efficacy for CPP screening, but BA advanced over chronological age and BMI was not useful for CPP screening.
Adolescent ; Body Mass Index ; Child ; Female ; Gonadotropin-Releasing Hormone ; Gonadotropins ; Humans ; Lutein ; Luteinizing Hormone ; Mass Screening ; Methods ; Puberty ; Puberty, Precocious ; Retrospective Studies ; Sensitivity and Specificity ; Treatment Outcome

Inhibin B is a gonadal hormone that downregulates the pituitary production of follicle-stimulating hormone (FSH). In recent years, inhibin B has proved to be an excellent marker of spermatogenesis and even a predictive factor for the recovery of fertility in patients undergoing orchiectomy and antineoplastic treatments. We propose to study inhibin B levels in orchiectomised testicular cancer patients, in order to identify a minimum value representative of normal semen quality. This retrospective study evaluates hormonal and semen parameters of 290 normozoospermic patients attending the Laboratory of Seminology - Sperm Bank "Loredana Gandini" (Rome, Italy) for cryopreservation of seminal fluid following a diagnosis of testicular cancer (TC group) and 117 healthy, normozoospermic men as a control group (CTR group). The percentile distribution of gonadotropin and inhibin B values in the TC and CTR groups was analyzed. There was a statistically significant difference between the two groups in the levels of all hormones (P ≤ 0.001) and in all semen parameters (P < 0.05). About 20% of TC patients revealed inhibin B levels below the 5^th percentile of CTR group, despite normozoospermia, and 31.4% had normal spermatogenesis in the presence of FSH values >95^th percentile of CTR group. Orchiectomised patients for testicular cancer presented inhibin B levels lower than healthy patients, despite normozoospermia. Our study revealed the poor sensitivity of the current inhibin B reference range when applied to monorchidic patients, suggesting the need to establish more representative ranges to enable more appropriate counseling in relation to the patient's new endocrine condition.
Adult ; Gonadotropins/blood* ; Humans ; Inhibins/blood* ; Male ; Orchiectomy ; Reference Values ; Testicular Neoplasms/surgery* ; Testosterone/blood* ; Young Adult

Hypogonadotropic hypogonadism (HH) is a rare disease in which medical treatment has a high success rate to achieve fertility. This study aimed to analyze the efficacy of hormone replacement therapy and determine predictive factors for successful spermatogenesis and spontaneous pregnancy in patients with idiopathic HH. A total of 112 patients with low testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and normal prolactin levels were diagnosed with HH and administered LH and FSH analogs as hormone replacement therapy. During treatment, 96 (85.7%) patients had sperm present in ejaculate samples. Among these patients, 72 were married and wanted a child. Of these 72 patients, 48 (66.7%) of couples had pregnancies from natural conception. After initiation of treatment, the mean time for the appearance of sperm in semen was 9.48 months. There were no significant differences between baseline FSH, T, and LH levels; however, older age, larger testicular size, and low rate of undescended testes were favorable factors for successful spermatogenesis. Larger testicular size and older age were also the main predictive factors for natural conception. We found that patients with undescended testes had a younger age, smaller testes, and lower T levels compared with patients exhibiting descended testes. The rate of sperm found in the ejaculate was not significantly decreased in patients with undescended compared with descended testis (73.7% vs 87.6%, P = 0.261). The medical approach for males with HH and azoospermia provides a successful treatment modality in regard to successful spermatogenesis and achievement of pregnancy.
Adolescent ; Adult ; Chorionic Gonadotropin/therapeutic use* ; Follicle Stimulating Hormone/therapeutic use* ; Gonadotropins/therapeutic use* ; Hormone Replacement Therapy/methods* ; Humans ; Hypogonadism/pathology* ; Luteinizing Hormone/therapeutic use* ; Male ; Middle Aged ; Retrospective Studies ; Spermatogenesis/drug effects* ; Young Adult