• Development and Reproduction
• /
• v.17 no.4
• /
• pp.469-475
• /
• 2013

In mammals, puberty is a process of acquiring reproductive competence, triggering by activation of hypothalamic kisspeptin (KiSS)-gonadotropin releasing hormone (GnRH) neuronal circuit. During peripubertal period, not only the external genitalia but the internal reproductive organs have to be matured in response to the hormonal signals from hypothalamic-pituitary-gonadal (H-P-G) axis. In the present study, we evaluated the maturation of male rat accessory sex organs during the peripubertal period using tissue weight measurement, histological analysis and RT-PCR assay. Male rats were sacrificed at 25, 30, 35, 40, 45, 50, and 70 postnatal days (PND). The rat accessory sex organs exhibited differential growth patterns compared to those of non-reproductive organs. The growth rate of the accessory sex organs were much higher than the those of non-reproductive organs. Also, the growth spurts occurred differentially even among the accessory sex organs; the order of prepubertal organ growth spurts is testis = epididymis > seminal vesicle = prostate. Histological study revealed that the presence of sperms in seminiferous tubules and epididymal ducts at day 50, indicating the puberty onset. The number of duct and the volume of duct in epididymis and prostate were inversely correlated during the experimental period. Our RT-PCR revealed that the levels of hypothalamic GnRH transcript were increased significantly on PND 40, suggesting the activation of hypothalamic GnRH pulse-generator before puberty onset. Studies on the peripubertal male accessory sex organs will provide useful references on the growth regulation mechanism which is differentially regulated during the period in androgen-sensitive organs. The detailed references will render easier development of endocrine disruption assay.

• Clinical and Experimental Reproductive Medicine
• /
• v.39 no.3
• /
• pp.95-106
• /
• 2012

It has been revealed that multiple cohorts of tertiary follicles develop during some animal estrous cycle and the human menstrual cycle. To reach developmental competence, oocytes need the support of somatic cells. During embryogenesis, the primordial germ cells appear, travel to the gonadal rudiments, and form follicles. The female germ cells develop within the somatic cells of the ovary, granulosa cells, and theca cells. How the oocyte and follicle cells support each other has been seriously studied. The latest technologies in genes and proteins and genetic engineering have allowed us to collect a great deal of information about folliculogenesis. For example, a few web pages (http://www.ncbi.nlm. nih.gov; http://mrg.genetics.washington.edu) provide access to databases of genomes, sequences of transcriptomes, and various tools for analyzing and discovering genes important in ovarian development. Formation of the antrum (tertiary follicle) is the final phase of folliculogenesis and the transition from intraovarian to extraovian regulation. This final step coordinates with the hypothalamic-pituitary-ovarian axis. On the other hand, currently, follicle physiology is under intense investigation, as little is known about how to overcome women's ovarian problems or how to develop competent oocytes from in vitro follicle culture or transplantation. In this review, some of the known roles of hormones and some of the genes involved in tertiary follicle growth and the general characteristics of tertiary follicles are summarized. In addition, in vitro culture of tertiary follicles is also discussed as a study model and an assisted reproductive technology model.

• Development and Reproduction
• /
• v.13 no.4
• /
• pp.207-215
• /
• 2009

Numerous factors can affect the activities of hypothalamus-pituitary-gonad (HPG) hormonal axis, resulting in alteration of reproductive capacity or status such as onset of puberty and menopause. Soon after the finding of leptin, a multifunctional hormone secreted from adipocytes, a close relationship between reproduction and body energy balance have been manifested. Ghrelin, another multifunctional hormone from gastrointestinal tract, is an endogenous ligand of growth hormone secretagogue receptor (GHSR), and is thought to be a counterpart of leptin in the regulation of energy homeostasis. As expected, ghrelin can also modulate the reproductive capacity through the modulation of activities of HPG axis. This paper summarizes the current knowledge on the discovery, gene structures, tissue distribution and roles of ghrelin and GHSRs in mammalian reproduction in particular modulation of reproductive hormone secretion in HPG axis. Like POMC gene expression in pituitary gland, preproghrelin gene can generate a complex repertoire of transcripts which further undergo alternative splicing and posttranslational modifications. Concerning the roles of preproghrelin gene products in the control of body physiology except energy homeostasis, limited knowledge is available so far. Several lines of evidence, however, show the interplay of ghrelin between metabolism and reproduction. In rat and human, the distribution of ghrelin receptor GHSRs (GHSR1a and GHSR1b) has been confirmed not only in the hypothalamus and pituitary which were originally postulated as target of ghrelin but also in the testis and ovary. Expression of the preproghrelin gene in the brain and gonads was also verified, suggesting the local role (s) of ghrelin in HPG axis. Ghrelin might play a negative modulator in the secretions of hypothalamic GnRH, pituitary gonadotropins and gonadal steroids though the action on pituitary is still questionable. Recent studies suggest the involvement of ghrelin in regulation of puberty onset and possibly of menopause entry. It is now evident that ghrelin is a crucial hormomal component in 'brain-gut' axis, and is a strong candidate links between metabolism and reproduction. Opposite to that for leptin, ghrelin signaling is likely representing the 'hunger' state of body energy balance and is necessary to avoid the energy investment into reproduction which has not a top priority in maintaining homeostasis. Further researches are needed to gain a deep insight into the more precise action mechanism and role of ghrelin in reproduction, and to guarantee the successful biomedical applications.

• Clinical and Experimental Pediatrics
• /
• v.65 no.4
• /
• pp.172-181
• /
• 2022

Pubertal onset is known to result from reactivation of the hypothalamic-pituitary-gonadal (HPG) axis, which is controlled by complex interactions of genetic and nongenetic factors. Most cases of precocious puberty (PP) are diagnosed as central PP (CPP), defined as premature activation of the HPG axis. The cause of CPP in most girls is not identifiable and, thus, referred to as idiopathic CPP (ICPP), whereas boys are more likely to have an organic lesion in the brain. ICPP has a genetic background, as supported by studies showing that maternal age at menarche is associated with pubertal timing in their offspring. A gain of expression in the kisspeptin gene (KISS1), gain-of-function mutation in the kisspeptin receptor gene (KISS1R), loss-of-function mutation in makorin ring finger protein 3 (MKRN3), and loss-of-function mutations in the delta-like homolog 1 gene (DLK1) have been associated with ICPP. Other genes, such as gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1), lin-28 homolog B (LIN28B), neuropeptide Y (NPYR), tachykinin 3 (TAC3), and tachykinin receptor 3 (TACR3), have been implicated in the progression of ICPP, although their relationships require elucidation. Environmental and socioeconomic factors may also be correlated with ICPP. In the progression of CPP, epigenetic factors such as DNA methylation, histone posttranslational modifications, and non-coding ribonucleic acids may mediate the relationship between genetic and environmental factors. CPP is correlated with short- and long-term adverse health outcomes, which forms the rationale for research focusing on understanding its genetic and nongenetic factors.

• Clinical and Experimental Pediatrics
• /
• v.46 no.4
• /
• pp.400-403
• /
• 2003

Congenital adrenal hyperplasia(CAH) is a recognized cause of precocious pseudopuberty. Some children with CAH also develop true precocious puberty with early maturation of the hypothalamic-pituitary-gonadal axis. We review a case of CAH who eventually developed central precocious puberty nine months after initial treatment with corticosteroid. A 3-year-old boy visited complaining of rapid growth, a large penis and frequent penile erections. This patient was diagnosed with CAH with elevated 17-OH progesterone and cortical hypertrophy of adrenal gland on CT scan. His gonadotropin levels were within the normal prepubertal range. Even on treatment with corticosteroid he grew rapidly and had testicular enlargement, pubic hair development and rapid bone maturation. At second admission, his gonadotropin levels were elevated both basally and in response to LHRH stimulation, suggesting that the CAH led to early activation of pubertal gonadotropin secretion(true precocious puberty). He was treated with monthly depot injections of a LHRH analog in addition to the hydrocortisone. His second sexual characteristics regressed gradually and rate of linear growth and bone maturation decreased.

• Advances in Traditional Medicine
• /
• v.10 no.2
• /
• pp.103-110
• /
• 2010

The seed powder of Abrus precatorius L. has traditionally been used as oral contraceptive agent by the women in some rural areas in Bangladesh. The present study aimed to examine the antifertility activity of A. precatorius seed extracts in experimental female rats. Finely ground seeds were extracted with aqueous acetone followed by successive partitioning with n-hexane, ethyl acetate (EtOAc), methanol (MeOH) and water. Water suspended crude seed powder, organic fractions of acetone extract and a standard contraceptive drug ($Nordette^{(R)}28$) were separately administered orally to the female rats for 30 days. n-Hexane, EtOAc and MeOH solubles at the doses of 2, 4 and 6 mg/rat/day, respectively and crude seed powder at 100 mg/rat/day exhibited 100% antifertility activity with lowest levels of serum luteinizing hormone (LH), follicle stimulating hormone (FSH) and $17{\beta}$-estradiol. Histological study of ovary and uterus of these rats exhibited reduced number of developing follicles and increased number of atretic follicles in the ovary, and fewer uterine glands with shrunken morphology, reduced endometrial height, poor vascularity and compact stroma in uterus. However, the activities of serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase and the body weight of the rats remained almost unaffected in all the seed extract treated rats compared to control. These results suggest that A. precatorius seed extracts reduced the levels of serum FSH, LH and $17{\beta}$-estradiol probably by affecting hypothalamic-pituitary-gonadal axis. The reduced levels of these hormones might have affected the oestrous cycle, follicular development, and subsequently the establishment of pregnancy in treated rats.

• Journal of Embryo Transfer
• /
• v.33 no.4
• /
• pp.305-311
• /
• 2018

Gonadotropin releasing hormone (GnRH) centrally plays a role in control of the hypothalamic-pituitary-gonadal axis-related hormone secretions in the reproductive neuroendocrine system. In addition, hormone receptors like luteinizing hormone receptor (LHR) are important element for hormones to take effect in target organ. However, ageing-dependent changes in terms of the distribution of GnRH neurons in the brain and LHR expression in the acyclic ovary have not been fully understood yet. Therefore, we comparatively investigated those ageing-dependent changes using young (1-5 months), middle (11-14 months) and old (21-27 months) aged female mice. Whereas a number of GnRH positive fibers and neurons with monopolar or bipolar morphology were abundantly observed in the brain of the young and middle aged mice, a few GnRH positive neurons with multiple dendrites were observed in the old aged mice. In addition, acyclic ovary without repeated development and degeneration of the follicles was shown in the old aged mice than others. LHR expression was localized in theca cells, granulosa cell, corpora lutea and atretic follicle in the ovaries from young and middle aged mice, in contrast, old aged mice had few positive LHR expression on the follicles due to acyclic ovary. However, the whole protein level of LHR was higher in the ovary of old aged mice than others. These results are expected to be used as an important basis on the relationship between GnRH and LHR in old aged animals as well as in further research for reproduction failure.

• Journal of Ginseng Research
• /
• v.47 no.3
• /
• pp.385-389
• /
• 2023

Background: Ginseng has been used as a traditional medicine for treatment of many diseases and for general health maintenance. Previously, we showed that ginseng did not demonstrate estrogenic property in ovariectomized mouse model. However, it is still possible that disruption of steroidogenesis leading to indirect hormonal activity. Methods: The hormonal activities were examined in compliance with OECD guidelines for detecting endocrine disrupting chemicals: test guideline (TG) No. 456 (an in vitro assay method for detecting steroidogenesis property) and TG No. 440 (an in vivo short-term screening method for chemicals with uterotrophic property). Results: Korean Red Ginseng (KRG) and ginsenosides Rb1, Rg1, and Rg3 did not interfere with estrogen and testosterone hormone synthesis as examined in H295 cells according to TG 456. KRG treatment to ovariectomized mice did not show a significant change in uterine weight. In addition, serum estrogen and testosterone levels were not change by KRG intake. Conclusion: These results clearly demonstrate that there is no steroidogenic activity associated with KRG and no disruption of the hypothalamic-pituitary-gonadal axis by KRG. Additional tests will be performed in pursuit of cellular molecular targets of ginseng to manifest mode of action.

• Development and Reproduction
• /
• v.13 no.3
• /
• pp.183-190
• /
• 2009

In mammals, puberty is a dynamic transition process from infertile immature state to fertile adult state. The neuroendocrine aspect of puberty is started with functional activation of hypothalamus-pituitary-gonadal hormone axis. The timing of puberty can be altered by many factors including hormones and/or hormone-like materials, social cues and metabolic signals. For a long time, attainment of a particular body weight or percentage of body fat has been thought as crucial determinant of puberty onset. However, the precise effect of high-fat (HF) diet on the regulation of hypothalamic GnRH neuron during prepubertal period has not been fully elucidated yet. The present study was undertaken to test the effect of a HF diet on the puberty onset and hypothalamic gene expressions in immature female rats. The HF diet (45% energy from fat, HF group) was applied to female rats from weaning to around puberty onset (postnatal days, PND 22-40). Body weight and vaginal opening (VO) were checked daily during the entire feeding period. In the second experiment, all animals were sacrificed on PND 36 to measure the weights of reproductive tissues. Histological studies were performed to assess the effect of HF diet feeding on the structural alterations in the reproductive tissues. To determine the transcriptional changes of reproductive hormone-related genes in hypothalamus, total RNAs were extracted and applied to the semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Body weights of HF group animals tend to be higher than those of control animals between PND 22 and PND 31, and significant differences were observed PND 32, PND 34, PND 35 and PND 36 (p<0.05). Advanced VO was shown in the HF group (PND $32.8{\pm}0.37$ p<0.001) compared to the control (PND $38.25{\pm}0.25$). The weight of ovaries (p<0.01) and uteri (p<0.05) from HF group animals significantly increased when compared to those from control animals. Corpora lutea were observed in the ovaries from the HF group animals but not in control ovaries. Similarly, hypertrophy of luminal and glandular uterine epithelia was found only in the HF group animals. In the semi-quantitative RT-PCR studies, the transcriptional activities of KiSS-1 in HF group animals were significantly higher than those from the control animals (p<0.001). Likewise, the mRNA levels of GnRH (p<0.05) were significantly elevated in HF group animals. The present study indicated that the feeding HF diet during the post-weaning period activates the upstream modulators of gonadotropin such as GnRH and KiSS-1 in hypothalamus, resulting early onset of puberty in immature female rats.

• Clinical and Experimental Pediatrics
• /
• v.49 no.3
• /
• pp.292-297
• /
• 2006

Purpose : In medulloblastoma, craniospinal radiation therapy combined with chemotherapy improves the prognosis of tumors but results in significant endocrine morbidities. We studied the endocrine morbidity, especially growth pattern changes. Methods : The medical records of 37 patients with medulloblastoma were reviewed retrospectively for evaluation of endocrine function and growth. We performed the growth hormone stimulation test in 16 patients whose growth velocity was lower than 4 cm/yr. Results : The height loss was progressive in most patients. The height standard deviation score (SDS) decreased from $-0.1{\pm}1.3$ initially to $-0.6{\pm}1.0$ after 1 year(P<0.01). Growth hormone deficiency(GHD) developed in 14 patients. During the 2 years of growth hormone(GH) treatment, the improvements of height gain or progressions of height loss were not observed. Twelve patients(32.4 percent) revealed primary hypothyroidism. One of six patients diagnosed with compensated hypothyroidism progressed to primary hypothyroidism. Primary and hypergonadotropic hypogonadism were observed in two and one patients respectively. There was no proven case of central adrenal insufficiency. Conclusion : Growth impairment developed frequently, irrespective of the presence of GHD in childhood survivors of medulloblastoma. GH treatment may prevent further loss of height. The impairment of the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-thyroidal axis is less common, while central adrenal insufficiency was not observed.