• Animal cells and systems
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• v.4 no.2
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• pp.173-179
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• 2000

Evidence suggested that atypical antipsychotics (APs) such as clozapine show less side effects than those of typical APs such as haloperidol and sulpiride. However, little is known about chronic effects of these drugs on changes in gonadotropin releasing hormone (GnRH) mRNA expression and luteinizing hormone (LH) immunoreactivity. Male rats were divided into water-, haloperidol-, sulpiride-, and clozapine-treated groups, and these drugs were administered orally for 4 weeks. The changes in the expression of GnRH mRNA and the LH immunoreactivity were determined in the hypothalamus and pituitary, respectively, using in situ hybridization and immunohistochemistry. GnRH mRNAs were clearly expressed in the water-treated control vats. This was significantly reduced by the chronic treatments with the typical APs, especially with haloperidol, but not with atypical APs clozapine. Likewise, LH immunoreactivity was clearly stained in the control group. While its immunoreativity was significantly reduced by the chronic APs treatments, clozapine treatment showed only slight attenuation. The results show that the atypical APs clozapine has less side effects in the gonadal function than the typical APs haloperidol and the sulpiride. These results suggest that clozapine is a safer drug than the typical APs, at least in the reproductive system.

• 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.

• The Journal of Korean Medicine
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• v.36 no.4
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• pp.150-155
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• 2015

The purpose of this report is to evaluate effect of Korean medical treatment on idiopathic gonadotropin-dependent precocious puberty (G-DPP) patient received herbal medicine. We administered Aesopjiyoun-tang remedy to idiopathic G-DPP and analyzed the delay effect by hormonal value and radiographs; the height growth effect by measurement of height. After Korean medical treatment, suppression effect to peak-Luteinizing Hormone level (LHL) is 14.39IU/L to 10.9IU/L for 13month, growth effect to height value is 11cm/13month; and change of mean growth velocity (MGV) is 6.08cm/year to 10.06cm/year. The gain in height by treatment is 3.98cm/year. The result suggests Aesopjiyoun-tang can be an effective treatment for G-DPP. Herbal medicine can be used as an alternative treatment in place of the GnRH treatment.

• Clinical and Experimental Reproductive Medicine
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• v.26 no.2
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• pp.157-161
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• 1999

Recent studies clearly demonstrated that the novel expression of LH gene in the rat testis, and suggested the local action of the LH-like molecule. The present study was performed to analyze the expression of LH genes in the rat accessory reproductive organs. Expression of LH subunit genes in the rat uterus and epididymis was demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) and specific LH radioimmunoassay (RIA). The $LH_{beta}$ transcripts in these organs contained the published cDNA structure, the pituitary type exons 1-3, which encoded the entire $LH_{beta}$ polypeptide. Presence of the transcripts for the ${\alpha}$-subunit in the rat reproductive tissues were also confirmed by RT-PCR. In the LH RIA, significant levels of LH were detected in crude extracts from the rat ovary, uterus and epididymis. The competition curves with increasing amount of tissue extracts were parallel with those of standard peptide, indicating that the immunoreactive LH-like materials in these tissues are similar to authentic pituitary LH molecule. In rat epididymis, the highest amount of immunoreactive LH was detected in corpus area. Our findings demonstrated that the genes for LH subunits are expressed in the rat accessory reproductive organs, and suggested that these extrapituitary LH may act as a local regulator with auto and/or paracrine manner.

• Clinical and Experimental Reproductive Medicine
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• v.26 no.3
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• pp.377-381
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• 1999

Objectives: Recent studies, including our own, demonstrated that the novel expression of LH gene in rat gonads and uterus, indicating that the local production and action of the LH-like molecule. In the present study, we investigated whether human uterus also expresses the LH gene. Design: Reverse transcription-polymerase chain reaction (RT-PCR) amplified the cDNA fragments coding $LH_{\beta}$ polypeptide from human endometrium but not from myometrium. Presence of the transcripts for the ${\alpha}$-subunit in human endometrium was also confirmed by RT-PCR. Results: Transcripts for $LH_{\beta}$ subunit were detected in endometrial samples from women with endometriosis. The gene for LH/hCG receptor was expressed in both endometrium and myometrium, showing good agreement with previous studies. Increased level of $LH_{\beta}$ transcript was determined in the endometrium from follicular phase compared to that from luteal phase. Conclusion: Taken together, our findings demonstrated that 1) the genes for LH subunits and LH/hCG receptor are expressed in human uterus, 2) the uterine LH expression was changed during menstrual cycle, suggesting that the uterine LH may playa local role in the control of uterine physiology and function(s).

• Development and Reproduction
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• v.26 no.1
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• pp.1-12
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• 2022

This study aimed to investigate the signal transduction of phosphorylation sites at the carboxyl (C)-terminal region of equine luteinizing hormone/chorionic gonadotropin receptor (eLH/CGR). The eLH/CGR has a large extracellular domain of glycoprotein hormone receptors within the G protein-coupled receptors. We constructed a mutant (eLH/CGR-t656) of eLH/CGR, in which the C-terminal cytoplasmic tail was truncated at the Phe656 residue, through polymerase chain reaction. The eLH/CGR-t656 removed 14 potential phosphorylation sites in the intracellular C-terminal region. The plasmids were transfected into Chinese hamster ovary (CHO)-K1 and PathHunter Parental cells expressing β-arrestin, and agonist-induced cAMP responsiveness was analyzed. In CHO-K1 cells, those expressing eLH/CGR-t656 were lower than those expressing eLH/CGR wild-type (eLH/CGR-wt). The EC₅₀ of the eLH/CGR-t656 mutant was approximately 72.2% of the expression observed in eLH/CGR-wt. The maximal response in eLH/CGR-t656 also decreased to approximately 43% of that observed in eLH/CGR-wt. However, in PathHunter Parental cells, cAMP activity and maximal response of the eLH/CGR-t656 mutant were approximately 173.5% and 100.8%, respectively, of that of eLH/CGR-wt. These results provide evidence that the signal transduction of C-terminal phosphorylation in eLH/CGR plays a pivotal role in CHO-K1 cells. The cAMP level was recovered in PathHunter Parental cells expressing β-arrestin. We suggest that the signal transduction of the C-terminal region phosphorylation sites is remarkably different depending on the cells expressing β-arrestin in CHO-K1 cells.

• Annals of Pediatric Endocrinology and Metabolism
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• v.23 no.4
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• pp.215-219
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• 2018

Purpose: We investigated the effect of overweight on luteinizing hormone (LH) levels after a gonadorelin stimulation test in Korean girls with idiopathic central precocious puberty (CPP). Methods: Medical records of 234 girls diagnosed with idiopathic CPP were reviewed retrospectively. CPP was diagnosed when the peak LH levels after gonadorelin stimulation was >5.0 U/L. The enrolled girls had a peak LH level >5.0 U/L after a gonadorelin stimulation test. Selected girls were classified as normoweight (body mass index [BMI] below the 85th percentile with respect to age) and overweight (BMI greater than the 85th percentile with respect to age). Results: The peak LH ($8.95{\pm}2.85U/L$ vs. $11.97{\pm}8.42U/L$, P<0.01) and peak folliclestimulating hormone ($9.60{\pm}2.91U/L$ vs. $11.17{\pm}7.77U/L$, P=0.04) after gonadorelin stimulation were lower in overweight girls with idiopathic CPP than in normoweight girls with idiopathic CPP. Being overweight was negatively associated with peak LH levels after gonadorelin stimulation test (odds ratio, 0.89; 95 % confidence interval, 0.81-0.98, P=0.02). Conclusion: In girls with idiopathic CPP, being overweight led to a lower LH peak after gonadorelin stimulation. Further research is needed to better understand the role of overweight on gonadotropin secretion in precocious puberty.

• Development and Reproduction
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• v.25 no.3
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• pp.133-143
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• 2021

In contrast to the human lutropin receptor (hLHR) and rat LHR (rLHR), very few naturally occurring mutants in other mammalian species have been identified. The present study aimed to delineate the mechanism of signal transduction by three constitutively activating mutants (designated M410T, L469R, and D590Y) and two inactivating mutants (D383N and Y546F) of the eel LHR, known to be naturally occurring in human LHR transmembrane domains. The mutants were constructed and measured cyclic adenosine monophosphate (cAMP) accumulation via homogeneous time-resolved fluorescence assays in Chinese hamster ovary (CHO)-K1 cells. The activating mutant cells expressing eel LHR-M410T, L469R, and D590Y exhibited a 4.0-, 19.1-, and 7.8-fold increase in basal cAMP response without agonist treatment, respectively. However, inactivating mutant cells expressing D417N and Y558F did not completely impaired signal transduction. Specifically, signal transduction in the cells expressing activating mutant L469R was not occurred with a further ligand stimulation, showing that the maximal response exhibited approximately 53% of those of wild type receptor. Our results suggested that the constitutively activating mutants of the eel LHR consistently occurred without agonist treatment. These results provide important information of LHR function in fish and regulation with regard to mutations of highly conserved amino acids in glycoprotein hormone receptors.

• Development and Reproduction
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• v.5 no.2
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• pp.175-180
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• 2001

The ectopic expression of gonadotropin releasing hormone(GnRH and luteinizing hormone(LH) in several tissues is a quite intriguing phenomenon. Recently, the presence of GnRH and its receptor has been clearly demonstrated in rodents and human mammary gland. In this context, one can postulate that the presence of local circuit composed of GnRH and LH in the gland. The present study was undertaken to elucidate whether there is a correlation between the LH expression in rat mammary gland and physiological status during the process of mammary differentiation. LH contents in mammary gland from cycling to weaning rats were measured by radioimmunoassay(RIA). In cycling rats, changes of the LH level in both serum and mammary gland showed similar pattern as the highest level in proestrus and the lowest level in diestrus II stage. While the serum LH levels were fluctuated from pregnant through involution stage, a sharp decline of mammary LH contents was observed in the lactating rats. This decrement was recovered in involuting rats to the level of proestrus stage. Reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analyses demonstrated that the transcriptional activities of the mammary LH and GnRH were increased from diestrus I stage to estrus stage, and the increased levels were maintained in pregnant, lactation and involution stages. To test the hypothesis that the alteration in mammary LH expression might be steroid-dependant, ovariectomy(OVX) and steroid supplement model was employed. As expected, supplement of estradiol(E$_2$) after OVX remarkably decreased serum LH level compared to that in serum from vehicle-only treated rats. Likewise, administration of E$_2$ significantly reduced the mammary LH content. The present study demonstrated that (i) the LH expression in mammary gland could be altered by some physiological parameters such as estrous cycle, pregnancy, lactation and involution, and (ii) ovarian steroid especially estrogen seems to be one of major endocrine factors which are responsible for regulation of mammary LH expression.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.3
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• pp.253-259
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• 2010

Objective: To evaluate if there is any correlation between the growth rate of dominant follicles and clinical characteristics or outcome variables in women undergoing controlled ovarian hyperstimulation (COH). Methods: This study was performed in 313 in vitro fertilization (IVF) cycles. Follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) were measured on day 3 of menstrual cycle, and serial ultrasonographic measurement of the diameter of growing follicles was performed. The growth rates of dominant follicles calculated by diameter difference divided by days were correlated with clinical characteristics and outcome variables. Results: There was no significant difference in the growth rate of the dominant follicles between gonadotropin releasing hormone (GnRH) agonist and antagonist cycles. No significant correlation was found between the growth rates and evaluated factors such as age, body mass index, LH, FSH, $E_2$, retrieved oocytes and fertilization rate. Conclusion: The Growth rate of dominant follicles seems to show an independent feature of basal characteristics and ovarian response.