• The Korean Journal of Pharmacology
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• v.29 no.2
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• pp.225-235
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• 1993

Pituitary LH release has been known to be regulated by the hypothalamic gonadotropin releasing hormone (GnRH) and the gonadal steroid hormones. In addition, neurotransmitters and neuropeptides are actively involved in the control of LH secretion. The alteration in LH release might reflect changes in biosynthesis and/or posttranslational processing of LH. However, little is known about the mechanism by which biosynthesis of LH subunits is regulated, especially at the level of transcription. In order to investigate if ovarian steroid hormones regulate the LH subunit gene expression, ${\alpha}\;and\;LH{\beta}$ steady state mRNA levels were determined in anterior pituitaries of ovariectomized rats. Serum LH concentrations and pituitary LH concentrations were increased markedly with time after ovariectomy. ${\alpha}\;and\;LH{\beta}$ subunit mRNA levels after ovariectomy were increased in a parallel manner with serum LH concentrations and pituitary LH contents, the rise in $LH{\beta}$ subunit mRNA levels being more prominent than the rise in ${\alpha}\;subunit$ mRNA. ${\alpha}\;and\;LH{\beta}$ subunit mRNA levels in ovariectomized rats were negatively regulated by the continuous treatment of ovarian steriod hormones for $1{\sim}4\;days$ and $LH{\beta}\;subunit$ mRNA seemed to be more sensitive to negative feedback of estradiol than progesterone. Treatment of estrogen antagonist, LY117018 or progesterone antagonist, RU486 significantly restroed LH subunit mRNA levels as well as LH release which were suppressed by estradiol or progesterone treatment. These results suggest that ovarian steroids negatively regulate the LH synthesis at the pretranslational level by modulating the steady state levels of ${\alpha}\;and\;LH{\beta}\;subunit$ mRNA and $LH{\beta}\;subunit$ mRNA seemed to be more sensitive to negative feedback action of estradiol than progesterone.

• Radiation Oncology Journal
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• v.15 no.4
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• pp.297-303
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• 1997

Purpose : To evaluate the prognostic factors for disease-free survival and long-term results of radiotherapy for pituitary adenoma. Methods and Materials : The study involved a retrospective review of out-come in a series of 27 patients with pituitary adenoma, between 1984 and 1995 at Paik hospital. The study included 20 patients treated with surgery and postoperative radiotherapy and 7 with radiotherapy alone. The patients were followed for 12-146 months (median : 97 months). Seventeen were men and 10 were women. The numbers of functioning and nonfunctioning pituitary adenorna were 22 and 5 respectively and those of microadenoma and macroadenoma were 4 and 23 respectively. The radiation doses of 5040-5580cGy (median : 5040cGy) were deliverd over 5-7 weeks, using 4MV LINAC. The prognostic factors were analyzed by log-rank test. Results: For radiation therapy alone, the 5YSR was 100% and progression free survival rate was 85.8%, The tumor was controlled in 6/7 (85.8%). For surgery and postoperative radiotherapy. the 5YSR, progression free survival rate and local control rate were 95%, 84.8%, and 89.5% respectively. The parameters of tumor size, hormone secretion, radiation dose. radiotherapy field size were evaluated in a uni- and multivariate analysis and all the factors were not statisticaIty significant (P>0.05). Eleven of 12 (92%) with visual field defect experienced normalization or improvement, and 5 for 7 evaluabie patients with hyperprolactinoma achived normalization in 4 and decrement in S patients. Only 2 patients developed mild degree of Panhypopituitarism. Conclusion: The radiotherapy appears to be effective in controiling clinical symptoms and signs resulting from pituitary adenoma. Local control rate with radiotherapy alone or with surgery and postoperative radiotherauy was comparable. There was a trend toward high recurrence rate in Patients with nonfunctioning or prolactin secretion tumor and larger radiation field sizes.

• Clinical and Experimental Reproductive Medicine
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• v.17 no.1
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• pp.29-44
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• 1990

In 105 patients with the past history of poor response to the previous controlled ovarian hyperstimulation(COH) due to poor follicular growth or premature LH surge, the effectiveness of pituitary suppression with gonadotropin-releasing hormone agonist(GnRH agonist) in IVF/GIFT program was evaluated in 112 cycles of COH using a combination regimen of Leuprolide acetate (Lupron TAP Pharmaceuticals, USA) and FSH/hMG or pure FSH from May to December, 1989 at SNUH. Starting on day 21 of the menstrual cycle(MCD #21, Day 1), Lupron (1.0mg/day, subcutaneous) was administered once a day till next MCD #3(suppression phase). After the confirmation of pituitary suppression, ovarian follicular growth was stimulated with FSH/hMG or pure FSH from MCD #3(Day + 1), and Lupron was continued with hMG or FSH until hCG administration (D 0) (stimulation phase). After suppression phase, serum E2 level decreased from 183.7${\pm}$95.1(Day 1) to 17.4${\pm}$12.3pg/ml (Day +1), and serum progesterone level from 19.17${\pm}$8.67 to 0.12${\pm}$0.05ng/ml. But there was no decresas in serum LH and FSH levels; LH from 12.74${\pm}$6.21 to 15.49${\pm}$4.93mIU/ml,FSH from 7.60${\pm}$3.84 to 8.58${\pm}$3.15 rnlU/ml. There was no occurrence of premature LH surge during COH. Eleven cycles(9.8%) were cancelled due to poor follicular growth during stimulation phase, and 3 cycles (3.0%) failed in the transvaginal oocytes fretrieval. Serum E2 level was 1366.8${\pm}$642.4 on D 0 and 1492.3${\pm}$906.9pg/ml on D+1. 7.00${\pm}$3.32 follicles(FD${\geq}$12mm) were observed on D 0, and 6.11${\pm}$4.15 oocytes were retrieved, with the oocyte retrieval rate per follicle of 95.0%. 3.59${\pm}$2.57 oocytes were fertilized and cleaved with the oocyte cleavage rate of 55.7%. In 83 IVF patients, 4.08${\pm}$2.39 embryos were transferred, and 16 pregnancies were obtained with the pregnancy rate per ET 2.39 mebryos were transferred, and 16 pregnancies were obtained with the pregnancy rate per ET of 19.3%. In 6 GIFT patients, 7.83${\pm}$3.31 oocytes were retrieved and transferred with maximum number of 6, but no pregnancy was obtained. When compared with the previous 108 cycles of COH using FSH/hMG or pure FSH regimen, the cancellation rate during COH was significantly decreased, and all the parameters of the outcome of COH including the pregnancy rate were increased. These data suggest that GnRH agonist therapy for pituitary suppression is an effective adjunct to the current gonadotropin regimens for COH in IVF/GIFT and can increase the probability of oocytes retrieval and pregnancy, especially in the previous poor responders.

• Development and Reproduction
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• v.9 no.1
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• pp.1-5
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• 2005

The hypothalamo-pituitary-gonadal hormone axis is centrally controlled by a complex regulatory network of excitatory and inhibitory signals, that is dormant during infantile and juvenile periods and activated at puberty. The kisspeptins are the peptide products of the KiSS-1 gene and the endogenous agonists for the G protein-coupled receptor 54(GPR54). Although KiSS-1 was initially discovered as a metastasis suppressor gene, a recent evidence suggests the KiSS-1/GPR54 system is a key regulator of the reproductive system. Yet the actual role of the KiSS-1/GPR54 system in the neuroendocrine control of gonadotropin secretion remains largely unexplored, the system could be the first missing link in the reproductive hormonal axis. Central or peripheral administration of kisspeptin stimulates the hypothalamic-pituitary-gonadal axis, increasing circulating gonadotropin levels in rodents, sheep, monkey and human models. These effects appear likely to be mediated via the hypothalamic GnRH neuron system, although kisspeptins may have direct effects on the anterior pituitary gland. The loss of function mutations of the GPR54(GPR54-/-) have been associated with lack of puberty onset and idiopathic hypogonadotropic hypogonadism(IHH). So kisspeptin infusion may provide a novel mechanism for HPG axis manipulation in disorders of the reproductive system.

• Development and Reproduction
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• v.15 no.3
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• pp.265-272
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• 2011

It is well known that adipose tissue or body fat has been proved as a crucial component of brain-peripheral axis which can modulate the activities of reproductive hormonal axis in female mammals including rodents and human. Concerning the male reproduction, however, the role of adipose tissue has not been thoroughly studied. The present study was carried out to elucidate the effect of a high-fat (HF) diet on the reproductive system of postpubertal male rats. The HF diet (45% energy from fat, HF group) was applied to male rats from week 8 after birth for 4 weeks. The blood glucose levels, body and tissue weights were measured. Histological studies were performed to assess the structural alterations in the reproductive tissues. To determine the transcriptional changes of reproductive hormone-related genes in hypothalamus and pituitary, total RNAs were extracted and applied to the semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Body weights (p<0.01) and blood glucose levels (p<0.01) of HF group were significantly higher than those of control animals. Similarly, the weights of epididymis (p<0.05), prostate (p<0.01), seminal vesicle (p<0.01) in HF group were higher than control levels. The weights of testis were not changed. The weights of kidney (p<0.001) and spleen (p<0.01) were significantly higher than control levels while the adrenal and pancreas weights were not changed. There were only slight alterations in the microstructures of accessory sex organs; the shape of luminal epithelial cells in epididymis from HF group were relatively thicker and bigger than those from control animals. In the semi-quantitative RT-PCR studies, the mRNA levels of hypothalamic GnRH (p<0.05) in HF group were significantly higher than those from the control animals. The mRNA levels of kisspeptin in HF group tend to be higher than control levels, the difference was not significant. Unlike the hypothalamic GnRH expression, the mRNA levels of pituitary $LH{\beta}$ and $FSH{\beta}$ were significantly decreased in HF group (p<0.05). The present study indicated that the 4-weeks feeding HF diet during the postpubertal period can alter the hypothalamus-pituitary (H-P) neuroendocrine reproductive system These results suggest that the increased body fat and the altered leptin input might disturb the H-P reproductive hormonal activities in male rats, and the changed activities seem to be responsible for the changes of tissue weights in accessory sex organs.

• Toxicological Research
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• v.20 no.3
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• pp.251-261
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• 2004

A large number of chemical pollutants including phthalates, alkylphenolic compounds and organochlorine pesticides have the ability to disrupt endocrine function in animals, and alter cog-nitive function. Because hormone mediated events play an important role in central nervous system development and function, the changes in cognitive function seem to be mediated by the endocrine-like action of these chemicals. The present study therefore was designed to investigate effect of bisphenol A (BPA), an endocrine disrupting chemical on neuro-behavial patterns, and expression of estrogen receptors and tyrosine hydroxylase, a limiting enzyme of dopamine synthesis pathway. BPA was treated orally for 3 weeks into 3 week old mice, and then the neuro-behavial patterns (stereo-type behaviors such as jumping rearing and forepaw tremor, climbing behavior, tail flick, rotarod and locomotor activity), and the expression of estrogen receptors and tyrosine hydroxylase were deter-mined every 3 week for 9 weeks. During the treatment of BPA, the food uptake and body weight increase were not significantly changed. BPA resulted in the increased stereotype behaviors (jump-ing, rearing and forepaw tremor) 6 or 9 weeks after treatment. The time response to tail flick and locomotor activity were decreased by the treatment of BPA, whereas the time for rotarod was increased by the treatment of BPA. The expression of estrogen receptor alpha and beta was increased in the brain and pituitary gland. Maximum expression was found in the brain after 9 week of 100 mg/kg BPA treatment and in the pituitary gland after 6 week of 100 mg/kg BPA treatment. Tyrosine hydroxylase was increased in dose and time dependent manners in the brain but no change was found in the pituitary gland. The present data show that exposure of BPA in the young mice could alter expression of estrogen receptors and dopamine synthesis pathway, thereby modulate neuro-behavial patterns (increase of stereotype behaviors but decrease locomotor activity).

• Korean Journal of Fisheries and Aquatic Sciences
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• v.32 no.2
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• pp.204-210
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• 1999

The present studies were conducted to evaluate the effects of activin-A on gonadotropins (GTHs) release in testosterone-treated immature rainbow trout Oncorhpynchus mykiss. The administration of testosterone elevated pituitary level of GTH II but not of GTH I. In this study using primary cultures of dispersed pituitary cells in static incubation, dose-dependent increases in GTH II release was observed in the activin-treated group at day 3 of incubation (long-term incubation), but not at day 1 of incubation (short-term incubation). Dopamine, a potent inhibitor of gonadotropin-releasing hormone (GnRH)-stimulated GTH II release in rainbow trout, was only partially effective in decreasing actvin-induced GTH II release. Furthermore, salmon GnRH (sGnRH)-stimulated GTH II release was not potentiated by the pretreatment with activin. However, the control mechanisms of GTH I release by activin and other hormones were not observed in the all tested experiments. The results of these studies support the contention that in contrast with the usual stimulatory effects of activin on GTH release in mammals, activin exerts long-term stimulatory actions on GTH II release in rainbow trout. The control mechanism of GTH I release, however, is a question that remains to be elucidated.

• Investigative Magnetic Resonance Imaging
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• v.22 no.2
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• pp.102-109
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• 2018

Purpose: The purpose of this study is to compare the performance of the T1 3D subtraction technique and the conventional 2D dynamic contrast enhancement (DCE) technique in diagnosing Cushing's disease. Materials and Methods: Twelve patients with clinically and biochemically proven Cushing's disease were included in the study. In addition, 23 patients with a Rathke's cleft cyst (RCC) diagnosed on an MRI with normal pituitary hormone levels were included as a control, to prevent non-blinded positive results. Postcontrast T1 3D fast spin echo (FSE) images were acquired after DCE images in 3T MRI and image subtraction of pre- and postcontrast T1 3D FSE images were performed. Inter-observer agreement, interpretation time, multiobserver receiver operating characteristic (ROC), and net benefit analyses were performed to compare 2D DCE and T1 3D subtraction techniques. Results: Inter-observer agreement for a visual scale of contrast enhancement was poor in DCE (${\kappa}=0.57$) and good in T1 3D subtraction images (${\kappa}=0.75$). The time taken for determining contrast-enhancement in pituitary lesions was significantly shorter in the T1 3D subtraction images compared to the DCE sequence (P < 0.05). ROC values demonstrated increased reader confidence range with T1 3D subtraction images (95% confidence interval [CI]: 0.94-1.00) compared with DCE (95% CI: 0.70-0.92) (P < 0.01). The net benefit effect of T1 3D subtraction images over DCE was 0.34 (95% CI: 0.12-0.56). For Cushing's disease, both reviewers misclassified one case as a nonenhancing lesion on the DCE images, while no cases were misclassified on T1 3D subtraction images. Conclusion: The T1 3D subtraction technique shows superior performance for determining the presence of enhancement on pituitary lesions compared with conventional DCE techniques, which may aid in diagnosing Cushing's disease.

• The Korean Journal of Zoology
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• v.33 no.2
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• pp.175-182
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• 1990

Progesterone production and oocyte maturation in ovarian follicles of Rana nigromaculata and Rana rugosa were investigated. Addition of frog pituitary homogenate (FPH) to the in utiro cultured follicles of R. nigromaculata stimulated a marked increase in the accumulation and secretion of progesterone (P$_4$) by the follicles and induced their oocyte maturation (germinal vesicle breakdown, GVBD) in a dose dependent manner. The FPH (0.1 pituitary equivalent/2 ml)-inducted P4 peak appeared in 3-6 hours and followed by the oocyte GVBD in 9-12 hours after the hormone stimulation. lncreae of intrafollicular cAMP levels with forskolin (an adenylatecyclase stimulator) and 3-isobutyl-1-methylxanthine (IBMX, a phosphodiesterase inhibitor) mimic the FPH action in the stimulation of P$_4$ production but not in the induction of oocyte maturation. The in uitro cultured follicies of R. rugosa behaved very differently from other amphibian follicles. Addition of FPH-(0. 1 pit. equivl2 ml) to the culture medium neither stimulated P$_4$ production by the follicles nor induced the oocyte GVBD. However, treatment of the follicles with forskolin and IBMX drastically stimulated both the intrafollicular accumulation (800 pg/follicle) and secretion (1700 pg/follicle) of P$_4$ by the follicles during culture period. Thus, the data suggest that the follicles are ready to respond to cAMP increase but not to the FPH stimulation in terms of P$_4$ production.

• Animal Bioscience
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• v.35 no.12
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• pp.1850-1859
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• 2022

Objective: The quantitative reverse transcription polymerase chain reaction (qPCR) is the most accurate and reliable technique for analysis of gene expression. Endogenous reference genes (RGs) have been used to normalize qPCR data, although their expression may vary in different tissues and experimental conditions. Verification of the stability of RGs in selected samples is a prerequisite for reliable results. Therefore, we attempted to identify the most stable RGs in the hypothalamic-pituitary-gonadal (HPG) axis in sows. Methods: The cycle threshold values of nine commonly used RGs (18S, HPRT1, GAPDH, RPL4, PPIA, B2M, YWHAZ, ACTB, and SDHA) from HPG axis-related tissues in the domestic sows in the different stages of estrus cycle were analyzed using two RG-finding programs, geNorm and Normfinder, to rank the stability of the pool of RGs. In addition, the effect of the most and least stable RGs was examined by normalization of the target gene, gonadotropin-releasing hormone (GnRH), in the hypothalamus. Results: PPIA, HPRT1, and YWHAZ were the most stable RGs in the HPG axis-related tissues in sows regardless of the stages of estrus cycle. In contrast, traditional RGs, including 18S and ACTB, were found to be the least stable under these experimental conditions. In particular, in the normalization of GnRH expression in the hypothalamus against several stable RGs, PPIA, HPRT1, and YWHAZ, could generate significant (p<0.05) elevation of GnRH in the preovulatory phase compared to the luteal phase, but the traditional RGs with the least stability (18S and ACTB) did not show a significant difference between groups. Conclusion: These results indicate the importance of verifying RG stability prior to commencing research and may contribute to experimental design in the field of animal reproductive physiology as reference data.