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

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

Pulsatile gonadotropin-releasing hormone (GnRH) may induce spermatogenesis in most patients with congenital hypogonadotropic hypogonadism (CHH) by stimulating gonadotropin production, while the predictors for a pituitary response to pulsatile GnRH therapy were rarely investigated. Therefore, the aim of our study is to investigate predictors of the pituitary response to pulsatile GnRH therapy. This retrospective cohort study included 82 CHH patients who received subcutaneous pulsatile GnRH therapy for at least 1 month. Patients were categorized into poor or normal luteinizing hormone (LH) response subgroups according to their LH level (LH <2 IU l^-1 or LH ≥2 IU l^-1) 1 month into pulsatile GnRH therapy. Gonadotropin and testosterone levels, testicular size, and sperm count were compared between the two subgroups before and after GnRH therapy. Among all patients, LH increased from 0.4 ± 0.5 IU l^-1 to 7.5 ± 4.4 IU l^-1 and follicle-stimulating hormone (FSH) increased from 1.1 ± 0.9 IU l^-1 to 8.8 ± 5.3 IU l^-1. A Cox regression analysis showed that basal testosterone level (β = 0.252, P = 0.029) and triptorelin-stimulated FSH_60min(β = 0.518, P = 0.01) were two favorable predictors for pituitary response to GnRH therapy. Nine patients (9/82, 11.0%) with low LH response to GnRH therapy were classified into the poor LH response subgroup. After pulsatile GnRH therapy, total serum testosterone level was 39 ± 28 ng dl^-1 versus 248 ± 158 ng dl^-1 (P = 0.001), and testicular size was 4.0 ± 3.1 ml versus 7.9 ± 4.5 ml (P = 0.005) in the poor and normal LH response subgroups, respectively. It is concluded that higher levels of triptorelin-stimulated FSH_60minand basal total serum testosterone are favorable predictors of pituitary LH response to GnRH therapy.
Adult ; Cohort Studies ; Follicle Stimulating Hormone/blood* ; Gonadotropin-Releasing Hormone/therapeutic use* ; Gonadotropins/blood* ; History, 16th Century ; Humans ; Hypogonadism/pathology* ; Luteinizing Hormone/blood* ; Male ; Pituitary Gland/pathology* ; Predictive Value of Tests ; Retrospective Studies ; Sperm Count ; Testis/pathology* ; Testosterone/blood* ; Treatment Outcome ; Triptorelin Pamoate/therapeutic use* ; Young Adult

OBJECTIVETo investigate the effects of hydro-alcoholic extract of Launaea acanthodes, a blood glucose lowering plant in folk medicine of Iran, on the structure of seminiferous tubules and serum gonadotropin and testosterone levels in hyperglycemic rats.

METHODSTwenty-four Wistar rats were randomly allocated into 4 groups (n=6): control, streptozotocin (STZ), STZ + insulin [STZ + Ins, 5 IU/(kg•day)], and STZ + Launaea acanthodes extract [STZ + Ext, 150 mg/(kg•day)]. Blood samples were collected at the 2nd and 4th weeks for detection of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) with enzyme-linked immuno sorbent assay (ELISA), and the right testes of rats were removed at the 7th week for the evaluation of diameter and wall thickness of seminiferous tubules and number of Leydig cells using unbiased stereological techniques.

RESULTSIn comparison with the control group, at the 2nd week FSH (0.45 vs 0.03, 0.02, 0.02 IU/L in STZ, STZ + Ins and STZ + Ext groups, respectively) and LH (1.02 vs 0.37, 0.2, 0.29 IU/L) showed significant decreases (all P<0.05) and testosterone (4.2 vs 8.37, 7.78, 11.8 ng/mL) showed a remarkable increase (all P<0.05). The levels of these hormones became closer in the STZ + Ext and the STZ + Ins groups to the control at the 4th week. A significant decrease in diameter and wall thickness of seminiferous tubules and number of Leydig cells were observed in the STZ group as compared with the control (P<0.01).

CONCLUSIONSAdministration of Launaea extract demonstrated a beneficial impact on the protection of testis from pathogenic and degenerative effects of hyperglycemia which may be partly due to its potential antioxidative effects.

Animals ; Asteraceae ; chemistry ; Blood Glucose ; metabolism ; Cell Count ; Cholesterol ; blood ; Ethanol ; chemistry ; Gonadotropins ; blood ; Hyperglycemia ; blood ; drug therapy ; pathology ; Insulin ; blood ; Leydig Cells ; drug effects ; pathology ; Lipoproteins ; blood ; Male ; Plant Extracts ; pharmacology ; therapeutic use ; Rats, Wistar ; Seminiferous Tubules ; drug effects ; pathology ; Testosterone ; blood ; Triglycerides ; blood ; Water ; chemistry

BACKGROUNDDelayed puberty can result either from constitutional delay of growth and puberty (CDP) or idiopathic hypogonadotropic hypogonadism (IHH). Gonadotropin-releasing hormone (GnRH) stimulation test has been generally accepted as a current method for diagnosing delayed puberty. The objective of this research was to assess the cut-off values and the efficacy of GnRH stimulation test in the diagnosis of delayed puberty in both males and females.

METHODSA study of 91 IHH, 27 CDP patients, 6 prepubertal children, and 20 pubertal adults was undertaken. Blood samples were obtained at 0, 30, 60, and 120 min after GnRH administration and the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured. For each parameter, the sensitivities and specificities were estimated, and the receiver operating characteristic (ROC) curves were constructed.

RESULTSThe ROC curves indicated that a serum basal LH <0.6 IU/L or peak LH <9.74 IU/L resulted in moderate sensitivity (73.8% or 80.0%) and specificity (90.9% or 86.4%) in the diagnosis of HH in males. Serum basal LH <0.85 IU/L or basal FSH <2.43 IU/L resulted in moderate sensitivity (80.0% or 100.0%) and specificity (75.0% or 50.0%) in the diagnosis of HH in females.

CONCLUSIONSOur data suggest that isolated use of the gonadorelin stimulation test is almost sufficient to discriminate between HH and CDP in males, but unnecessary in females. The most useful predictor is serum basal or peak LH to differentiate these two disorders in males, but serum basal LH or FSH in females.

Adolescent ; Female ; Follicle Stimulating Hormone ; blood ; Gonadotropin-Releasing Hormone ; pharmacology ; Gonadotropins ; deficiency ; Humans ; Hypogonadism ; blood ; diagnosis ; Hypothalamus ; drug effects ; Luteinizing Hormone ; blood ; Male ; Pituitary Gland ; drug effects ; Puberty, Delayed ; blood ; diagnosis ; Sensitivity and Specificity

OBJECTIVETo study the effects of valproate sodium (VPA) on the level and axle of pituitary gonadotropin in adolescent girls with epilepsy.

METHODSTwenty-three adolescent girls with epilepsy aged from 8 to 14 years were treated with VPA for 1 year. The levels of serum pituitary gonadotropin including estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin and testosterone were measured before treatment and 3 months, 6 months and 1 year after treatment.

RESULTSThe serum levels of estradiol, follicle-stimulating hormone, luteinizing hormone and prolactin in the children with epilepsy were not significantly different during the 1 year VPA treatment compared with pretreatment. However, the serum level of testosterone was reduced 1 year after treatment (0.4±0.3 ng/mL) compared with pretreatment (0.7±0.4 ng/mL) and 3 months after treatment (0.7±0.4 ng/mL) (P<0.05).

CONCLUSIONSVPA treatment for 1 year does not increase serum levels of androgen in adolescent girls with epilepsy, suggesting that VPA is an ideal choice of treatment for the girls.

Adolescent ; Anticonvulsants ; therapeutic use ; Child ; Epilepsy ; blood ; drug therapy ; Female ; Gonadotropins, Pituitary ; blood ; Humans ; Valproic Acid ; therapeutic use

The authors report a case of acute kidney injury (AKI) resulting from menstruation-related disseminated intravascular coagulation (DIC) in an adenomyosis patient. A 40-yr-old woman who had received gonadotropin for ovulation induction therapy presented with anuria and an elevated serum creatinine level. Her medical history showed primary infertility with diffuse adenomyosis. On admission, her pregnancy test was negative and her menstrual cycle had started 1 day previously. Laboratory data were consistent with DIC, and it was believed to be related to myometrial injury resulting from heavy intramyometrial menstrual flow. Gonadotropin is considered to play an important role in the development of fulminant DIC. This rare case suggests that physicians should be aware that gonadotropin may provoke fulminant DIC in women with adenomyosis.
Acute Kidney Injury/*diagnosis/etiology ; Adult ; Creatinine/blood ; Disseminated Intravascular Coagulation/*chemically induced/complications ; Endometriosis/*complications/diagnosis/surgery ; Female ; Fertilization in Vitro ; Gonadotropins/*adverse effects ; Humans ; Magnetic Resonance Imaging ; Menstruation/*physiology ; Uterus/pathology/surgery

OBJECTIVETo investigate the relationship of plasma ghrelin and adenohypophyseal hormone levels in female precocious puberty.

METHODSA total of 84 patients aged from 6 to 9 years were enrolled in this study. They were divided into idiopathic central precocious puberty (ICPP) and premature thelarche(PT)groups according to their secondary sexual characteristics, bone age, volumes of uterus and ovary, and results of GnRH test. Plasma ghrelin levels were measured by radioimmunoassay. ACTH, TSH, PRL, GH, LH and FSH were measured by chemoluminescence technique.

RESULTSGhrelin levels in ICPP group were Log (2.42+/-0.26) ng/L, which were significantly lower than those in PT group and controls [Log (2.62+/-0.21) ng/L and Log (2.58+/-0.44) ng/L, respectively, P<0.05]. However there was no significant difference between PT group and controls(P>0.05). Ghrelin levels of ICPP girls with Tanner III were Log (2.31+/-0.24) ng/L, significantly lower than those of ICPP girls with Tanner II [Log (2.53+/-0.24) ng/L, P<0.05]. By bivariate correlation analysis, ghrelin levels in precocious puberty girls were negatively correlated with ACTH, PRL and LH15, LH30 and LH60 in GnRH test(r=-0.248, -0.235, -0.445, 0.405, 0.398, respectively, P<0.05). No significant correlation was found between ghrelin and GH, LH0(-2), FSH0(-2), and FSH15, FSH30 and FSH60 in GnRH test.

CONCLUSIONICPP girls have lower plasma ghrelin levels, which are decreased with the development of Tanner stage. The plasma ghrelin levels are negatively correlated with ACTH, PRL and LH.

Adrenocorticotropic Hormone ; blood ; Child ; Female ; Ghrelin ; blood ; Gonadotropins, Pituitary ; blood ; Humans ; Luteinizing Hormone ; blood ; Puberty, Precocious ; blood

OBJECTIVETo analyse the heritabilities of serum luteinizing hormone(LH), follicle-stimulating hormone (FSH), testosterone (T) and estradiol (E2) in twin boys, and to study the genetic contributions to gonadotropin-gonadal axis.

METHODSA total of 51 pairs of male twins, 35 monozygotic (MZ) and 16 dizygotic(DZ) aged 5 to 11 years, were investigated. Serum gonadotropin and sex hormone were measured by radioimmunoassay. The twin zygosity was verified by determination of short tandem repeat amplified fragment length polymorphism systems. The genetic analysis was performed using intraclass correlation coefficient method.

RESULTSThe intraclass correlation coefficient was greater in the MZ twins than in the DZ twins. The estimated heritabilities were respectively LH 0.51, FSH 0.32, T 0.81, E2 0.41.

CONCLUSIONGenetic factors are major determinants of gonadotropin-gonadal axis in boys.

Child ; Child, Preschool ; Gonadal Steroid Hormones ; blood ; Gonadotropins ; blood ; Humans ; Male ; Radioimmunoassay

OBJECTIVETo assess the diagnostic value of the simplified gonadorelin stimulation test for precocious puberty.

METHODSTwo hundred and ninety-two girls with signs of advanced breast development received the gonadorelin stimulation test. According to the result of gonadorelin stimulation test, the girls were divided into 3 groups: 151 with central precocious puberty (CPP),119 with premature thelarche (PT) and 22 with peripheral precocious puberty (PPP).

RESULTSLH or FSH levels at 15 min, 30 min, 60 min in PPP group were not significantly different (P>0.05). Those were significantly different in PT group (P<0.01). The highest levels of LH were at 30 min and the highest levels of FSH were at 60 min. LH or FSH levels at 15 min, 30 min, 60 min in CPP group were significantly different (P<0.01) with the highest levels at 30 min. The ratio of basal LH and FSH >0.2 had a diagnostic sensitivity of 48.3 % and specificity of 69.7%. Taking the LH/FSH ratio >0.9 at 15 min, 30 min, 60 min as cut-off value, the diagnostic sensitivity was 80.1%, 68.9% and 38.4%, and the specificity was 90.8%, 96.6% and 69.7%, respectively.

CONCLUSIONThe LH/FSH ratio>0.9 at 15 min after gonadorelin stimulation test can be used as a cut-off value to differentiate CPP from PT and blood sample at 60 min were not necessary.

Child ; Female ; Follicle Stimulating Hormone ; blood ; Gonadotropin-Releasing Hormone ; Gonadotropins ; blood ; Humans ; Luteinizing Hormone ; blood ; Predictive Value of Tests ; Puberty, Precocious ; diagnosis ; Sensitivity and Specificity