• Title/Summary/Keyword: Hypothalamus-pituitary-gonad axis

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The Consequences of Mutations in the Reproductive Endocrine System

  • Choi, Donchan
    • Development and Reproduction
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    • v.16 no.4
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    • pp.235-251
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    • 2012
  • The reproductive activity in male mammals is well known to be regulated by the hypothalamus-pituitary-gonad axis. The hypothalamic neurons secreting gonadotropin releasing hormone (GnRH) govern the reproductive neuroendocrine system by integrating all the exogenous information impinging on themselves. The GnRH synthesized and released from the hypothalamus arrives at the anterior pituitary through the portal vessels, provoking the production of the gonadotropins(follicle-stimulating hormone (FSH) and luteinizing hormone (LH)) at the same time. The gonadotropins affect the gonads to promote spermatogenesis and to secret testosterone. Testosterone acts on the GnRH neurons by a feedback loop through the circulatory system, resulting in the balance of all the hormones by regulating reproductive activities. These hormones exert their effects by acting on their own receptors, which are included in the signal transduction pathways as well. Unexpected aberrants are arised during this course of action of each hormone. This review summarizes these abnormal phenomena, including various mutations of molecules and their actions related to the reproductive function.

Expression of Maturation-Related Genes and Leptin during Sexual Maturation in the Female Goldfish: Effects of Exogenous Kisspeptin

  • Kim, Na Na;Choi, Young Jae;Oh, Sung-Yong;Choi, Cheol Young
    • Journal of Marine Life Science
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    • v.1 no.1
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    • pp.41-49
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    • 2016
  • Kisspeptin (Kiss) and its cognate receptor, kisspeptin receptor (KissR; G protein coupled receptor 54, GPR54), have recently been recognized as potent regulators of reproduction in teleosts. Additionally, leptin plays an important role in energy homeostasis and reproductive function in teleosts. The purpose of this study was to examine differences in the concentration of the hormones of the Kiss/KissR system and leptin and the expression of their underlying genes, all of which are involved in the sexual maturation of female goldfish, Carassius auratus, following treatment with Kiss. The expression levels of KissR increased after the Kiss injection. Furthermore, the peptide hormone leptin also increased after the injection (in vivo and in vitro). Additionally, the expression of GnRH and GTHs (GTHα, FSHβ, and LHβ) increased in the brain and pituitary (in vitro and in vitro). These results support the hypothesis that Kiss plays important roles in the direct regulation of the hypothalamus-pituitary-gonad axis and leptin in goldfish. Therefore, we suggest that Kiss system gene expression is correlated with energy balance and reproduction.

Role of Ghrelin in the Control of Reproductive Endocrine Function (포유류 생식 내분비 기능 조절에서 Ghrelin의 역할)

  • Lee, Sung-Ho
    • Development and Reproduction
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    • v.13 no.4
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    • pp.207-215
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    • 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.

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Changes in Sex Hormone-related Gene Expression in Zebrafish Dario rerio by the Administration of Sexual Maturation Inhibitors (성 성숙 억제 물질 투여에 따른 Zebrafish Dario rerio의 성호르몬 관련 유전자 발현 변화)

  • Kim, Ki-hyuk;Moon, Hye-na;Yeo, In-kyu
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.55 no.1
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    • pp.17-22
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    • 2022
  • Successful reproduction in vertebrates necessitates complex interactions along the brain-pituitary-gonad axis, it is determined by gonadotropin releasing hormone produced in the hypothalamus of the brain, gonadotropin synthesized in the pituitary gland, and sex hormone secreted by the gonads. The goal of this study was to secure and test technology for controlling (inhibiting) sexual maturation hormones such as maturation hormones through hormone regulation. We studied the effect on sexual maturation of zebrafish Danio rerio by tamoxifen, anastrozole, exemestane and dopamine 4 kinds of sexual maturation inhibitors to feed and after administration. As a result, 4 kinds of sexual maturation inducing substances were mixed with zebrafish feed, it could be concluded that all of them were effective in inhibiting sexual maturation by reducing mRNA levels of genetic materials related to sexual maturation.

Role of Serotonin in Reproduction (생식현상에서의 세로토닌의 역할)

  • Lee, Sung-Ho
    • Development and Reproduction
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    • v.5 no.1
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    • pp.9-16
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    • 2001
  • Biogenic monoamines are divided into three categories; catecholamines(dopamine, norepinephrine, and epinephrine), indoleamine(serotonin and melatonin) and histamine. Among them, serotonin has been intensively studied by many researchers with a broad spectrum of biomedical interests. A concise overview of serotonin-related topics such as biosynthetic pathway, receptor subtypes, and roles in reproduction will be provided. In particular, serotonergic efffect on the regulation of hypothalamus-pituitary-gonad hormonal axis and sexual behaviors will be emphasized. Though our Knowledge on the biological roles and its clinical applications are still limited, these topics are quite promising subjects which will be helpful for improving our 'quality of life' in near future.

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Effect of 6-Hydroxydopamine (6-OHDA) on the Expression of Hypothalamus-Pituitary Axis Hormone Genes in Male Rats (수컷 흰쥐의 시상하부-뇌하수체 축 호르몬 유전자 발현에 미치는 6-Hydroxydopamine(6-OHDA)의 영향)

  • Heo, Hyun-Jin;Ahn, Ryun-Sup;Lee, Sung-Ho
    • Development and Reproduction
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    • v.13 no.4
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    • pp.257-264
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    • 2009
  • A neurotoxin, 6-hydroxydopamine (6-OHDA) has been widely used to create animal model for Parkinson's disease (PD) due to its specific toxicity against dopaminergic (DA) neurons. Since DA signals modulate a broad spectrum of CNS physiology, one can expect profound alterations in neuroendocrine activities of both PD patients and 6-OHDA treated animals. Limited applications of 6-OHDA injection model, however, have been made on the studies of hypothalamuspituitary neuroendocrine circuits. The present study was performed to examine whether blockade of brain catecholamine (CA) biosynthesis with 6-OHDA can make any alteration in the transcriptional activities of hypothalamus-pituitary hormone genes in adult male rats. Three-month-old male rats (SD strain) were received 6-OHDA ($200{\mu}g$ in $10{\mu}\ell$ of saline/animal) by intracerebroventricular (icv) injection, and sacrificed after two weeks. To determine the mRNA levels of hypothalamuspituitary hormone genes, total RNAs were extracted and applied to the semi-quantitative RT-PCRs. The mRNA levels of tyrosine hydroxylase (TH), the rate-limiting enzyme for the catecholamine biosynthesis, were significantly lower than those from the control group (control:6-OHDA=1:0.72${\pm}$0.02AU, p<0.001), confirming the efficacy of 6-OHDA injection. The mRNA levels of gonadotropin-releasing hormone (GnRH) and corticotropin releasing hormone (CRH) in the hypothalami from 6-OHDA group were significantly lower than those from the control group (GnRH, control:6-OHDA=1:0.39${\pm}$0.03AU, p<0.001; CRH, control:6-OHDA=1:0.76${\pm}$0.07AU, p<0.01). There were significant decreases in the mRNA levels of common alpha subunit of glycoprotein homones (Cg$\alpha$), LH beta subunit (LH-$\beta$), and FSH beta subunit (FSH-$\beta$) in pituitaries from 6-OHDA group compared to control values (Cg$\alpha$, control:6-OHDA=1:0.81${\pm}$0.02AU, p<0.001; LH-$\beta$, control:6-OHDA=1:0.68${\pm}$0.04AU, p<0.001; FSH-$\beta$, control:6-OHDA=1:0.84${\pm}$0.05AU, p<0.001). Similarly, the level of adrenocorticotrophic hormone (ACTH) transcripts from 6-OHDA group was significantly lower than that from the control group (control: 6-OHDA=1:0.86${\pm}$0.04AU, p<0.01). The present study demonstrated that centrally injected DA neurotoxin could downregulate the transcriptional activities of the two hypothalamus-pituitary neuroendocrine circuits, i.e., GnRH-gonadotropins and CRH-ACTH systems. These results suggested that hypothalamic CA input might affect on the activities of gonad and adrenal through modulation of hypothalamus-pituitary function, providing plausible explanation for frequent occurrence of sexual dysfunction and poor stress-response in PD patients.

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Changes in Plasma Steroid Hormone Level in Rockfish (Sebastes inermis) by the Controlled Water Temperature and Photoperiod (수온과 광주기 조절에 의한 볼락 (Sebastes inermis)의 혈장내 성 스테로이드호르몬 농도의 변화)

  • CHANG Young Jin;LIM Han Kyu;KWON Joon Yeong
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.34 no.1
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    • pp.13-16
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    • 2001
  • Plasma levels of sex steroid hormones in rockfish, Sebastes inermis were examined monthly in relation to gonadosomatic index (GSI) under a controlled water temperature and photoperiod, The GSI of a control group (C) in female began to increase from November and reached a maximum in January, Sample fish under a controlled water temperature and photoperiod (Tr) were divided into a responded group (Tr-r) and a un-responded group (Tr-n) by the gonadal maturation condition and GSI. The GSI of females in Tr-r reached a maximum in March. But the female GSI in Tr-n kept lower than 1.2 during the experimental period. No differences in male GSI were noticed between C and Tr. The $estradiol-17\beta$ and testosterone levels of female plasma in Tr reached a maximum in October, later than those in C. In males, these was no difference in 11-ketotestosterone and testosterone between C and Tr. When rockfish was reared in September under the controlled water temperature and photoperiod which were equivalent to those in July, that is two months earlier, the maturation of females was delayed in comparison with C. This finding suggested that delayed maturation in ovary was caused by the secretion of sex steroid hormones in relation to the water temperature and photoperiod of the hypothalamus-pituitary-gonad axis.

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Temporal Changes of c-fos, c-jun, and Heat Shock Protein 25 mRNA in Rat Uterus following Estradiol Treatment (Estrogen 처리에 따른 흰쥐 자궁조직내 c-fos, c-jun, hsp25 mRNA 발현 변화)

  • Lee, Young-Ki;Kim, Sung-Rye
    • Clinical and Experimental Reproductive Medicine
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    • v.26 no.2
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    • pp.149-156
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    • 1999
  • Steroid hormone is known to cause the dynamic changes of mammalian uterus during reproductive cycle, which are modulated via hypothalamus-pituitary -gonad reproductive endocrine axis. Although there were so many studies about estrogenic regulation of uterine growth and differentiation. There is little information about the effect of estrogen on the expression of various transcription factors involved in gene expression. Thus the present study was designed to demonstrate E induced expression of c-fos, c-jun, hsp25 mRNA in rat uterus. Employing Northern blot analysis, we studied the temporal expressions of c-fos, c-jun, and hsp25 messenger RNAs (mRNAs) elicited by a single 17beta-estradiol (E) treatment in the uteri of bilaterally ovariectomized adult rats. c-fos, c-jun, and hsp25 mRNA levels were increased and peaked at 3h after E administration, and then c-fos and c-jun mRNA levels were rapidly decreased to basal control level while, increased hsp25 mRNA levels were sustained till 12h post E treatment. To test the estrogenic effect on the increase of c-fos, c-jun, and hsp25 mRNA levels, we also examined the effects of antiestrogen (tamoxifen). Pretreatment with tamoxifen effectively blocked the E-induced increase of c-fos, c-jun, and hsp25 mRNA levels at 3h post E treatment. Present results suggest that transient increase of c-fos and c-jun protooncogene mRNA at the early time and simultaneous expression of hsp25 mRNA contribute to the response of uterine tissues to E in adult female rats.

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Clinical Characteristics of precocious puberty girls and Comparison Analysis of GnRH Test results with Diagnosis type (성조숙증 여아들의 임상적 특징 및 진단별 성선자극호르몬 분비호르몬 GnRH (Gonado Tropin Releasing Hormone) 검사결과의 비교분석평가)

  • Kim, Jung-In;Kwon, Won-Hyun;Moon, Ki-Choon;Lee, In-Won
    • The Korean Journal of Nuclear Medicine Technology
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    • v.20 no.2
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    • pp.54-61
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    • 2016
  • Purpose Precocious Puberty is defined as the development of secondary sexual characteristics in girls younger than 8 years, and boys 9 years. Cause premature closure of the epiphysis is a disease that eventually decreases the final adult height. In this study, we retrospectively analyzed to evaluate the diagnostic difference the GnRH (Gonado-tropin-releasing Hormone) stimulation test results with medical records of precocious puberty in girls. Materials and Methods From February 2015 to December 2015 it was enrolled in the girls 118 people who visited the Seoul National University Bundang Hospital, Pediatrics, Endocrinology Internal Medicine. True precocious puberty group (n=57), early puberty group (n=39), were divided into Premature thelarche (n=22) group. A Tanner stage, chronological age, bone age, height, body weight for each group was determined by examining the mean${\pm}$standard deviation. GnRH test result was compared LH (Basal, 30 min, 45 min, 60 min), FSH (Basal, 30 min, 60 min) for each group, Each group LH, FSH Peak value distribution, the mean${\pm}$standard deviation was calculated for the peak LH/LH basal ratio, peak LH/Peak FSH ratio. The significance probability (P-value) between the value of each third group was determined. Results The average height of the true precocious puberty group $131{\pm}14.85$, the mean weight was $28.80{\pm}4.93$, the average chronological age $7.1{\pm}0.81$, the mean bone age was $9.9{\pm}0.9$, The average height of early puberty group was $134{\pm}5.10$, the average weight $28.50{\pm}4.43$, the average chronological age $8.05{\pm}0.03$, the mean bone age was $10.0{\pm}0.62$, The average height of Premature thelarche $129{\pm}6,01$, the average weight was $28.65{\pm}5.98$, the average chronological age $7.02{\pm}0.58$, the mean bone age was $8.04{\pm}1.29$. There was no significant difference when compared to the height and weight. There was a significant difference between the groups in the chronologic age and bone age difference (P <0.0002) True precocious puberty group showed peak LH levels at 30'(82.5%), 45'(12.3%), 60'(5.3%), in Peak FSH 30'(8.8%), 60'(91.2%). Early Puberty group showed high values in Peak LH at 30'(79.5%), 45'(17.9%), 60'(2.6%), in peak FSH levels at 30'(7.7%), 60'(92.32%). In Premature thelarche Group it showed the Peak LH levels at 30'(30%), 45'(59%), 60'(9.09%), Peak FSH levels at 30'(0%) 60'(100%). When compared with the The Peak LH/basal LH ratio, True precocious puberty group was $19.09{\pm}17.15$, early puberty group was $15.23{\pm}10.88$, Premature thelarche group showed significant differences between the three groups as $4.93{\pm}4.36$.(P <0.0001) LH Peak/FSH Peak ratio, true precocious puberty group was $1.222{\pm}0.77$, early puberty group was $1.34{\pm}1.23$, Premature thelarche group showed significant differences between the three groups as $0.3{\pm}0.09$(P <0.0001) Conclusion In order to diagnose the true precocious puberty have a diagnostic value when the LH peak after GnRH stimulation is increased by more than two to three times compared to baseline or a predetermined level or more than 5~10 IU/L increases. GnRH Test is a test for a long time and the patient discomfort due to repeated blood sampling, but the hypothalamus-pituitary gland- gonad axis activity evaluate and is the most basic accurate test in the differential diagnosis of precocious puberty disorders.

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