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

OBJECTIVETo assess the effect of repeated gonadotropic stimulations on the developmental potential and growth differentiation factor-9 (GDF-9) expression of mouse oocytes.

METHODSFemale Kunming mice were treated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (HCG) for 3 times, and the control mice were treated with normal saline. The two groups of mice were both stimulated subsequently to obtain the mature oocytes. Immunocytochemical staining was employed to evaluate GDF-9 expression in the oocytes. The oocytes were then inseminated and cultured till the formation of blastocysts to compare the cleavage rate and blastocyst formation rate between the groups.

RESULTSA total of 253 mature oocytes were obtained in the repeated stimulation group, with a mean of 11.5 oocytes from each mouse; 521 mature oocytes were obtained in the control group with a significantly greater mean number of 32.6 from each mouse (P<0.05). The average optical density and integrated optical density for GDF-9 expression were significantly lower in the oocytes in repeated stimulation group than in the control group (P<0.05 and 0.01, respectively). After insemination, the cleavage rate were comparable between repeated stimulation group and the control group (85.6% vs 88.8%), but the blastocyst formation rate was significantly lower in repeated stimulation group (20.8% vs 35.2%, P<0.01).

CONCLUSIONRepeated gonadal stimulation decreases the developmental potential of mouse oocytes possibly due to reduced GDF-9 expression.

Animals ; Cells, Cultured ; Female ; Gonadotropins ; pharmacology ; Growth Differentiation Factor 9 ; metabolism ; Mice ; Oocytes ; cytology ; growth & development ; metabolism ; Ovulation Induction ; adverse effects ; methods

OBJECTIVETo evaluate the influence of superovulation by GnRHa protocol and pregnant mare's serum gonadotropin (PMSG) alone on the expression of estrogen receptor (ER), progesterone receptor (PR) and leukemia inhibitory factor (LIF) mRNA on endometrium.

METHODSForty-five female ICR mice were randomly allocated into 3 groups:(1) GnRHa+PMSG group: alarelin was give first for desensitizing the pituitary, then superovulation with PMSG; (2) PMSG group: mice were injected with PMSG only; (3) Natural cycle group: mice were given with same volume of saline. Endometrium samples were taken at 48 hours after given hCG or ovulation (control group). ER and PR in glandular cells were detected with SP immunohistochemistry semiquantitatively. Expression of LIF mRNA on endometrium was detected with reverse transcriptase-polymerase chain reaction (RT-PCR) analysis.

RESULTThe positive rate(%) and expression intense (AU) of ER and PR on glandular epithelium cells were significantly lower in GnRHa+PMSG group and PMSG group than those in natural cycle group (all P <0.01). The expression of LIF mRNA was significantly lower in GnRHa+PMSG group and PMSG group than that in natural cycle group (all P <0.01); but the expressions of ER, PR and LIF in GnRHa+PMSG group were higher than those in PMSG group.

CONCLUSIONThe protocol with GnRHa down regulates the expressions of ER, PR and the LIF mRNA on the mice of secretive phase endometrium, suggesting it may have an adverse effect on the endometrial receptivity in mice, but it may still be better than PMSG alone.

Animals ; Clinical Protocols ; Endometrium ; metabolism ; Female ; Gonadotropin-Releasing Hormone ; analogs & derivatives ; pharmacology ; Gonadotropins ; pharmacology ; Leukemia Inhibitory Factor ; metabolism ; Mice ; Mice, Inbred ICR ; Ovulation Induction ; methods ; RNA, Messenger ; metabolism ; Random Allocation ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Superovulation ; metabolism

OBJECTIVE: One of the models we study is the ovarian granulosa cell (GC), a somatic cell lineage that is critically important for maintenance of the female germ line and many endocrine functions of the ovaries. The objective of this study is to clarify the significance of ceramide and the role of ceramide metabolism in dictating the fate of cells exposed to stress. METHODS: We first treated GC with a C8-ceramide analog or an amine derivative of ceramide that cannot be metabolized by ceramidase (C8-ceramine). Northern blot analysis was performed to evaluate mRNA of acid ceramidease expression regualted by gonadotropin and in situ hybridization was done to identify the mRNA expression of acid ceramidase in ovaries. RESULTS: After 6 hours, C8-ceramide (50 micro M) triggered apoptosis in only 28 +/- 6% of the cells, whereas C8-ceramine (50 micro M) induced apoptosis in all cells (LD50=1 micro M). These data suggested that ceramidase activity is a critical determinant of GC survival. In situ hybridization showed that mRNA of acid ceramidase was highly expressed in GC in growing follicle. mRNA of acid ceramidase was expressed abundantly in granulosa cells and ovaries and its expression was significantly increased by gonadotropin in granulosa cells in in situ hybridization. Forty two hour after gonadotropin treatment, mRNA expression of acid ceramidase in granulosa cells was two fold increased cells comparing with no treatment control in northern blot analysis (P<0.05). In copora lutea, elevated mRNA expression of acid ceramidase was decreased. CONCLUSION: We concluded that GC possess inherently high levels of ceramidase activity, and that ceramidase has important for metabolizing ceramind to maintain GC survival in the ovary.
Acid Ceramidase ; Apoptosis ; Blotting, Northern ; Cell Lineage ; Ceramidases* ; Female ; Germ Cells ; Gonadotropins ; Granulosa Cells* ; Humans ; In Situ Hybridization ; Metabolism ; Ovary ; RNA, Messenger

The aim of hormonal male contraception is to prevent unintended pregnancies by suppressing spermatogenesis. Hormonal male contraception is based on the principle that exogenous administration of androgens and other hormones such as progestins suppress circulating gonadotropin concentrations, decreasing testicular Leydig cell and Sertoli cell activity and spermatogenesis. In order to achieve more complete suppression of circulating gonadotropins and spermatogenesis, a progestin has been added testosterone to the most recent efficacy trials of hormonal male contraceptives. This review focusses on the potential effects of male hormonal contraceptives on cardiovascular risk factors, lipids and body composition, mainly in the target group of younger to middle-aged men. Present data suggest that hormonal male contraception can be reasonably regarded as safe in terms of cardiovascular risk. However, as all trials have been relatively short (< 3 years), a final statement regarding the cardiovascular safety of hormonal male contraception, especially in long-term use, cannot be made. Older men with at high risk of cardiovascular event might not be good candidates for hormonal male contraception. The potential adverse effects of hormonal contraceptives on cardiovascular risk appear to depend greatly on the choice of the progestin in regimens for hormonal male contraceptives. In the development of prospective hormonal male contraception, data on longer-term cardiovascular safety will be essential.
Age Factors ; Androgens/therapeutic use* ; Antispermatogenic Agents ; Cardiovascular Diseases/epidemiology* ; Contraceptive Agents, Male/therapeutic use* ; Gonadotropins/metabolism* ; Humans ; Male ; Progestins/therapeutic use* ; Testosterone/therapeutic use*

OBJECTIVETo study the effect of Bushen Tiaojing Recipe (BTR) and Xiaoyao Pill (XP) on cathepsin-L (Cat-L) mRNA in mice.

METHODSImmature mice were randomly divided into the normal group, the control group, the BTR group and the XP group, three in each group. Cat-L mRNA expression in mice was detected using reverse transcription polymerase chain reaction (RT-PCR) at 0, 4, 8 and 12 h after injecting 5 IU (human chorionic gonadotropin, HCG).

RESULTSCat-L mRNA expression increased gradually after HCG injection, the relative levels in the control group at 0, 4, 8 and 12 h were 0.066 +/- 0.005, 0.383 +/- 0.045, 0.737 +/- 0.024 and 1.036 +/- 0.073 respectively, comparisons between different time-points showed significant difference (P < 0.01). Compared with the control group, the Cat L mRNA expression was higher at 4 h in both BTR and XP groups (P < 0.01), at 8 h in the XP group (P < 0.05), and at 12 h in BTR group after injecting HCG (P < 0.05). Compared with the control group, cat L mRNA expression showed no statistic difference at 8 h in BTR group and at 12 h in XC group.

CONCLUSIONSBTR promoted the ovulation by enhancing the expression of CatL gene, and that of XP by advancing the peak of CatL gene expression.

Animals ; Cathepsin L ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Female ; Gonadotropins ; administration & dosage ; Humans ; Mice ; Mice, Inbred Strains ; Ovulation ; drug effects ; RNA, Messenger ; genetics

The effect of angiotensin II (Ang II) on the follicular development was studied by using an animal model of follicular atresia induced by pregnant mare s serum gonadotropin (PMSG). The results showed that: (1) a large number of atretic follicles were found in the ovary of 24-day-old mouse after 6-day treatment of PMSG. Deoxyribonucleic acid (DNA) extracted from granulosa cells clearly showed a ladder band under agarose gel electrophoresis analysis. (2) the contents of Ang II in the ovary extremely increased with the development of follicular atresia. (3) Ang II significantly antagonized the stimulating effect of the follicle-stimulating hormone (FSH) on estradiol (E(2)) generation of granulosa cells. It is suggested that Ang II may be involved in the regulation of follicular atresia in mouse.
Angiotensin II ; pharmacology ; physiology ; Animals ; Cells, Cultured ; Estradiol ; biosynthesis ; Female ; Follicle Stimulating Hormone ; pharmacology ; Follicular Atresia ; physiology ; Gonadotropins, Equine ; pharmacology ; Granulosa Cells ; drug effects ; metabolism ; Mice

Gonadotropin-releasing hormone (GnRH) and dopamine (DA) can stimulate growth hormone (GH) release, but their effects on GH mRNA synthesis are controversial and deficient in fish. Orange-spotted grouper (Epinephelus coioides) is a hermaphroditic marine fish with sex reversal. Few data are available concerning the regulation of GH in grouper. In the present study, the effects of GnRH and DA on GH release and GH mRNA expression were determined using pituitary fragments of orange-spotted grouper under static culture conditions. After incubation from 1 h to 24 h, salmon GnRH (sGnRH, 100 nmol/L) stimulated the release of GH and increased the level of GH mRNA time-dependently. The minimum duration of sGnRH effect was 1 h. Both of sGnRH and mammalian GnRH (mGnRH) augmented the release of GH and the level of GH mRNA in a dose-dependent manner. The potency of sGnRH on both GH release and GH mRNA level was more pronounced than that of mGnRH. The effects of 1 micromol/L APO (Apomorphine), an agonist of D(1)/ D(2) dopamine receptors, significantly stimulated GH release and GH mRNA synthesis after incubation for 12 h. APO stimulated GH release and GH mRNA abundance in a dose-dependent manner. These results demonstrate that both GnRH and DA directly stimulate GH release and GH mRNA expression at the pituitary level, the actions of GnRH are more potent than that of DA in orange-spotted grouper.
Animals ; Dopamine ; pharmacology ; Gene Expression Regulation ; Gonadotropin-Releasing Hormone ; pharmacology ; Gonadotropins, Pituitary ; metabolism ; Growth Hormone ; biosynthesis ; genetics ; secretion ; Perciformes ; genetics ; metabolism ; Pituitary Gland ; cytology ; metabolism ; Pituitary Hormone-Releasing Hormones ; secretion ; RNA, Messenger ; biosynthesis ; genetics

Conservative treatment with high doses of progestin is an alternative to standard hysterectomy for young patients with early-stage endometrial adenocarcinoma who desire to preserve their fertility. Here we report a patient with well-differentiated early-stage endometrial adenocarcinoma and poor fertility potential who failed to become pregnant in two in vitro fertilization-embryo transfer cycles and suffered a relapse after conservative treatment. This case illustrates that assessment of fertility potential is critical at the time of initial evaluation and conservative treatment planning for patients with endometrial adenocarcinoma.
Adenocarcinoma ; drug therapy ; metabolism ; Adult ; Antineoplastic Agents, Hormonal ; Endometrial Neoplasms ; drug therapy ; metabolism ; Female ; Follicle Stimulating Hormone ; therapeutic use ; Gonadotropins ; therapeutic use ; Humans ; Infertility ; Pregnancy ; Progesterone ; therapeutic use ; Reproductive Techniques, Assisted

OBJECTIVETo observe the effects of calcium phosphate cement/eucommia ulmoides extracts compound (CPC/EUE) on cell proliferation and adhesion of MC3T3E1 osteoblasts in vitro.

METHODSCultured MC3T3E1 osteoblasts were divided into 5 groups: blank control, CPC/EUE 0, 0.152, 0.304 and 0.608 mg/ml. 3H-TdR and scan electronic microscopy (SEM) were used to observe the cell growth, proliferation and adhesion.

RESULTThe CPC/EUE compound enhanced the cell growth, proliferation and adhesion. The concentrations of 0.152 mg/ml, 0.304 mg/ml were more significant in enhancing the cell proliferation rate (P<0.05).

CONCLUSIONCPC/EUE can promote the cell growth, proliferation and adhesion of the osteoblasts.

Alkaline Phosphatase ; metabolism ; Bone Cements ; Calcium Phosphates ; pharmacology ; Cell Adhesion ; radiation effects ; Cell Differentiation ; radiation effects ; Cell Proliferation ; radiation effects ; Cells, Cultured ; Gonadotropins ; metabolism ; Humans ; Osteoblasts ; cytology ; drug effects ; Tissue Adhesions