• The Korean Journal of Pharmacology
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• v.23 no.2
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• pp.57-75
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• 1987

Two modalities of gonadotropin secretion, pulsatile gonadotropin and preovulatory gonadotropin surge, have been identified in the mammals. Pulsatile gonadotropin secretion is modulated by the pulsatile pattern of GnRH release and complex ovarian steroid feedback actions. The neural mechansim that regulates the pulsatile release of GnRH in the hypothalamus is called "GnRH pulse generator". Ovarian steroids, estradiol and progesterone, appear to exert thier feedback effects both directly on the pituitary to modulate gonadotropin release and on a hypothalamic site to modulate GnRH release; estradiol primarily affects the amplitude while progesterone decreases the frequency of the pulsatile GnRH. Steroid hormones are known to affect catecholamine transmission in brain. MBH-POA is richly innervated by NE systems and close apposition of NE terminals and GnRH cell bodies occurs in the MBH as well as in the POA. NE normally facilitates pulsatile LH release by acting through ${\alpha}-receptor$ mechanism. However, precise nature of facilitative role of NE transmission in maintaining pulsatile LH has not been clearly understood. Close apposition of DA and GnRH terminals in ME might permit DA to influence GnRH release. Action of DA transmission probably is mediated by axo-axonic contacts between GnRH and DA fibers in the ME. Dopamine transmission does not normally regulate pulsatile LH release, but under certain conditions, increased DA transmission inhibit LH pulse. Endogenous opioid acts to suppress the secretion of GnRH into hypophysial portal circulation, thereby inhibiting gonadotropin secretion. However, an interaction between endogenenous opioid peptides and gonadotropin release is a complex one which involves ovarian hormones as well. LH secretion appears to be most suppressed by endogenenous opioids during the luteal phase, at a time of elevated progesterone secretion. The arcuate nucleus contains not only cell bodies for GnRH and ${\beta}-endorphin$ but also a dense aborization of fibers suggesting that GnRH release is changed by the interactions between GnRH and ${\beta}-endorphin$ cell bodies within the arcuate nucleus. The frequency and amplitude of pulsatile LH release seem to be increased during the preovulatory gonadotropin surge. Estradiol exerts positive feedback action on the hypothalamo-pituitary axis to trigger preovulatory LH surge. GnRH is also crucial hormonal stimulus for preovulatory LH surge. It is unlikely, however, that increased secretion of GnRH during the preovulatory gonadotropin surge represents an obligatory neural signal for generation of the LH discharge in primates including human. Modulation of preovulatory LH surge by catecholamines has been studied almost exclusively in rats. NE and E may be involved in distinct way to accumulate GnRH in the MBH and its release into the hypophysial portal system during the critical period for LH surge on proestrus in rats. However, the mechanisms whereby augmented adrenergic transmission may facilitate the formation and accumulation of GnRH in the ME-ARC nerve terminals before the LH surge have not been clearly understood.

• Animal cells and systems
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• v.4 no.3
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• pp.287-292
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• 2000

The present work examined the role of gonadotropin-releasing hormone (GnRH) and dopaminergic drugs on the secretion of maturational gonadotropin (GTH II) in relation to testosterone m treatment. This study provides evidence that the plasma GTH II levels are increased by T treatment in precocious males, but not in the immature animal. In addition, GnRH analogue (GnRHa) alone significantly increased the plasma GTH II secretion in immature rainbow trout treated with T, as well as in T-treated and T-untreated precocious males. However, injection with either dopamine (DA) or domperidone (DOM; DA D2 receptor antagonist) alone did not alter the basal plasma GTH 11 secretion in all experimental groups. The secretion of GTH II in the T-treated precocious males was remarkably influenced by GnRHa or combination of dopaminergic drugs. Notably, the effects of dopaminergic drugs on GnRHa-induced GTH II secretion w8s prolonged by T in precocious males. In T-treated immature animals, GnRHa-induced GTH II secretion was Increased only by a dose DOM (10$\mu$g/g body n) but not by higher dose DOM (100$\mu$/g body wt). In the T-untreated immature rainbow trout, however, plasma GTH 11 secretion was not influenced by the same treatments. Therefore, these results indicate that DA may be acting indirectly by blocking the effect of GnRH on GTH II secretion in vivo. T may act to modulate the relative contribution by the stimulatory (GnRH) and inhibitory (DA) neuroendocrine factors, which would ultimately determine the pattern of GTH II secretion.

• Journal of Embryo Transfer
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• v.33 no.4
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• pp.297-304
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• 2018

The purpose of the present study was to determine the elaborate characteristics of ovarian changes including follicles and corpus luteum, and hormonal patterns of gonadotropin surge mode secretions during the normal consecutive estrous cycle in three dairy cows. Non-lactating and multiparous Holstein cows (n=3) used as experimental animals. The cows were assigned to examine the relationship among ovarian changes (follicle, corpus luteum), ovarian steroids (estradiol, progesterone) and gonadotropin (LH, FSH) surge mode secretion during the successive estrous cycles by rectal palpation, ultrasonography and hormonal assay. The mean length of the estrous cycle for the three cows was $23.1{\pm}1.44days$ (${\pm}SEM$), with a range of 20-28 days. In six estrous cycles, the number of two follicular waves, three follicular waves and four follicular waves was 2, 3 and 1, respectively. The sequential ultrasonographic monitoring showed that the corpus luteum with ${\geq}10mm$ in diameter detected from Day 2 (Day 0 is ovulation) in six estrous cycles of all cows. Preovulatory increases in estradiol concentration reached $10.36{\pm}1.10pg/ml$ on the 2 days before ovulation of the last dominant follicle. All cows exhibited a preovulatory rise in estradiol concentration followed by a typical preovulatory LH and FSH surge. The mean interval from the peak of LH/FSH surge to ovulation of the last dominant follicle was $31.3{\pm}1.76h$ (${\pm}SEM$). In these results, each dairy cow showed that ovarian morphological changes and gonadotropin surge mode secretion will be regulated by various environmental factors including age, breeds, nutrition, breeding conditions, etc.

• The Korean Journal of Zoology
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• v.39 no.3
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• pp.266-272
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• 1996

Experiments were carried out to ascertain whether gonadotropin or a phorbol ester (12-O-tetradecanoyl phorbol-13-acetate, TPA) induces oocyte ovulation and stimulates prostaglandin synthesis by Rana ovarian follicles in vitro. Rana nigromaculata collected from underground in spring were utilized for the present experiment. Treatment of frog pituitary homogenate (FPH) or TPA to ovarian fragments in culture induced oocyte ovulation in a dose dependent manner and stimulated prostaglandin F2a (PGF$_2$$\alpha$ synthesis. Both treatruents were more effective in inducing the ovulation and PGF$_2$$\alpha$ secretion by the follicles obtained in May than those in April. A Protein kinase C inactivator, 1-(5-isoquinolinyl-sulfonyl)-2-methyl-piperazine (H-7), or cyclooxygenase inhibitor, indomethacin (IM) suppressed the FPH- or TPA-induced PGF$_2$$\alpha$ production, but IM failed to suppress the FPH- or TPA-induced ovulation. Time course of oocyte ovulation and PGF$_2$$\alpha$ secretion by FPH and TPA treatments were very similar to each other. FPH stimulated progesterone secretion by the follicle but TPA failed to do so. Taken together, the data presented here suggest that protein kinase C (PKC) in follicle play a role in the ovulation process of Rana nigromaculata, probably via prostaglandin synthesis.

• Journal of Life Science
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• v.11 no.2
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• pp.103-107
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• 2001

The equine chorionic gonadotropin (eCG) subunits $\alpha$ and ${\beta}$ are transcribed from different genes and associate noncovalently to form the bioactive eCG heterodimer. Dimerization is rate limiting for eCG secretion, and dissociation leads to hormone inactivation. The correct conformation of the heterodimer is alto important for efficient secretion, hormone-specific post-translational modifications, receptor binding and signal transduction. To determine whether ${\alpha}$ and ${\beta}$ subunits can be synthesized as a single polypeptide chain (tethered-eCG) and also display biological activity, the tethered-eCG molecule by fusing the carboxyl terminus of the eCG ${\beta}$-subunit to the amino terminus of the af-subunit was construe-ted and transfected into chinese hamster ovary (CHO-Kl) cells. LH- and FSH-like activities were assayed in terms of testosterone production and aromatase activity in primary cultured rat Leydig cells and granulosa cells, respectively. The tethered-eCG was efficiently secreted and showed similar LH-like activity to the dimeric eCG ${\alpha}$/${\beta}$ and native eCG. FSH-like activity of the tethered-eCG was also shown similarly in comparison with the native and wild type eCG ${\alpha}$/${\beta}$. Our data for the first time suggest that the tethered-eCG can be expressed efficiently and the produced product by the CHO-K1 cells is fully LH- and FSH-like activities in rat in vitro bioassay system. Our results also suggest that this molecular can imply particular models of FSH-like activity not LH-like activity in the eCG. Taken together, these data indicate that the constructs of tethered molecule will be useful in the study of mutants that affect subunit association and/or secretion.

• Korean Journal of Animal Reproduction
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• v.26 no.4
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• pp.395-399
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• 2002

Human chorionic gonadotropin (hCG) is a member of the glycoprotein hormone family which includes FSH. hCG TSH. These hormone family is characterized by a heterodimeric structure composed a common $\alpha$-subunit noncovalently linked to a hormone specific $\beta$-subunit. To determine u and $\beta$ -subunits can be synthesized as a single polypeptide chain (tethered-hCG) and also display biological activity, the tethered-hCC and -FSH molecule by fusing the carboxyl terminus of the hCG $\beta$-subunit to the amino terminus of the $\alpha$-subunit was constructed. To determine the importance of $\alpha$ COOH -terminal amino acid, we also deleted the $\alpha$ COOH-terminal amino acids. The expressing vectors were transfected into CHO-K 1 cells. The tethered-wthCG and -wtFSH was efficiently secreted. The $\alpha$ Δ83hCG and $\alpha$ Δ 83FSH mutants had no secretion. These results are the first conclusive evidence that COOH-terminal amino acids are very important for secretion in human glycoprotein hormone $\alpha$-subunit. These results demonstrated that the $\alpha$ Δ83hCG and $\alpha$ Δ 83FSH mutants could be play a pivotal role in the secretion of tethered-molecule.

• Fisheries and Aquatic Sciences
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• v.3 no.1
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• pp.37-43
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• 2000

We used a mammalian GnRH antagonist, $[Ac-3,4-dehydro-Pro^1,\;D-p-F-Phe^2,\;D-Trp^{3.6}]$-GnRH, to examine the details of the salmon type gonadotropin-releasing hormone (sGnRH) and GnRH agonist analog $(Des-Gly^{10}$[d-Ala^6]-ethylamide GnRH; GnRHa) functions in the control of maturational gonadotropin (GTH II) secretion, in precocious male rainbow trout, in both in vivo and in vitro experiments. In the in vivo study, plasma GTH II levels increased by sGnRH or GnRHa treatment, but the response was more rapid and stronger in the GnRHa treatment group. The increase in GTH II was significantly suppressed by the GnRH antagonist, while the antagonist had no effect on basal GTH II levels in both groups. The GnRH antagonist showed stronger suppression of GTH II levels in the sGnRH treatment fish than in the GnRHa treatment fish. In addition, plasma androgenic steroid hormones (testosterone and 11-ketotestosterone) increased by the sGnRH or GnRHa treatment. The GnRH antagonist significantly inhibited the increases in plasma androgenic steroid hormone levels stimulated by the sGnRH or GnRHa, while the antagonist had no effect on basal androgenic steroid hormone levels in both groups. In the in vitro study, treatment with sGnRH or GnRHa increased GTH II release from the cultured dispersed pituitary cells, but the response was stronger in the GnRHa treatment group. The increase in GTH II release by GnRH was suppressed by adding the GnRH antagonist, dose­dependently. On the other hand, basal release of GTH II did not decrease by the GnRH antagonist treatment in both groups. These results suggest that the GnRH antagonist, $[Ac-3,4-dehydro-Pro^1,\;D-p-F-Phe^2,\;D-Trp^{3.6}]-GnRH$, used in this study is effective in blocking the action of GnRH-induced GTH II release from the pituitary gland both in vivo and in vitro.

• 대한생식의학회:학술대회논문집
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• 2002.11a
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• pp.91-91
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• 2002

• Asian-Australasian Journal of Animal Sciences
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• v.20 no.7
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• pp.1039-1048
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• 2007

Two experiments were conducted to determine whether leptin is a metabolic signal for gonadotropin secretion in ewes. In the first experiment, twenty-eight cyclic Chal ewes were assigned randomly to an energy restricted, no leptin group (ERNL) (60% of maintenance; n = 14) and an energy normal, no leptin group (ENNL) (100% of maintenance; n = 14) for 71 days (6 estrous cycles). Estrus was synchronized with seven consecutive injections of $PGF_{2{\alpha}}$ Biweekly, body weight (BW) and body condition score (BCS) were determined and blood samples were collected to measure plasma leptin concentration. Blood samples were also taken to determine plasma progesterone concentration twice weekly. After each PG injection from the second injection to the end of experiment, four ewes were selected and blood samples were collected at 20 minutes and at hourly intervals for 3 h to detect plasma LH and FSH concentration. In the second experiment, after the ceasing of the estrous cycle caused by energy restriction, six acyclic ewes were selected and randomly allotted to two groups (n = 3) and received the following treatment for four days. Ewes in an energy restricted, leptin group (ERL) were fed with a ration which provided 60% of maintenance energy requirements and intravenously injected with $4{\mu}g$ leptin/kg BW daily. Ewes in an energy excess, no leptin group (EENL) were fed with a ration that provided 180% (120%+60%) of maintenance energy requirements and intravenously injected with 1 ml saline daily. In both groups, blood samples were collected at 20 minutes and at hourly intervals for 3 h before feeding on d 0 and d 5, and for 3 h before and after injections as above on d 2 and d 4 to detect plasma LH and FSH concentration. In the first experiment, BW and BCS from the $2^{nd}$ estrous cycle, and leptin from the $3^{rd}$ estrous cycle to the end of the experiment significantly (p<0.05) decreased. In ERNL ewes, mean plasma concentrations of FSH significantly (p<0.01) decreased from the $4^{th}$ estrous cycle to d 71 and LH pulsatile secretion was suppressed on d 71, so that, mean plasma concentrations of LH (p<0.05), LH pulse frequency (p<0.01) and LH pulse amplitude (p<0.05) significantly decreased. In the second experiment, injection of leptin significantly increased mean circulating concentrations of LH (p<0.05), LH pulse frequency (p<0.01), LH pulse amplitude (p<0.05) and mean circulating concentrations of FSH (p<0.01) and leptin (p<0.01). High energy intake significantly (p<0.05) stimulated pulsatile secretion of LH and leptin secretion (p<0.01), but non-significantly increased plasma FSH concentration. The results of this study indicate that leptin is a metabolic signal for the GnRH-LH/FSH axis in feed-restricted fat-tailed ewes.

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