Congenital lipoid adrenal hyperplasia

Congenital lipoid adrenal hyperplasia (lipoid CAH) is the most fatal form of CAH, as it disrupts adrenal and gonadal steroidogenesis. Most cases of lipoid CAH are caused by recessive mutations in the gene encoding steroidogenic acute regulatory protein (StAR). Affected patients typically present with signs of severe adrenal failure in early infancy and 46,XY genetic males are phenotypic females due to disrupted testicular androgen secretion. The StAR p.Q258X mutation accounts for about 70% of affected alleles in most patients of Japanese and Korean ancestry. However, it is more prevalent (92.3%) in the Korean population. Recently, some patients have been showed that they had late and mild clinical findings. These cases and studies constitute a new entity of 'nonclassic lipoid CAH'. The cholesterol side-chain cleavage enzyme, P450scc (CYP11A1), plays an essential role converting cholesterol to pregnenolone. Although progesterone production from the fetally derived placenta is necessary to maintain a pregnancy to term, some patients with P450scc mutations have recently been reported. P450scc mutations can also cause lipoid CAH and establish a recently recognized human endocrine disorder.

Advances in the study of steroidal inhibitors of cytochrome P45017alpha / 药学学报

The steroidal enzyme cytochrome P45017alpha catalyzes the conversion of progesterone and pregnenolone into androgens, androstenedione and dehydroepiandrosterone, respectively, the direct precursors of estrogens and testosterone. Dihydrotestosterone is the principal active androgen in the prostate, testosterone is also an active stimulant of the growth of prostatic cancer tissue. Inhibition of this enzyme as a mechanism for inhibiting androgen biosynthesis could be a worthwhile therapeutic strategy for the treatment of PCA. In this paper, four categories of steroidal inhibitors of cytochrome P45017alpha will be reviewed, a diverse range of steroidal inhibitors had been synthesized and shown to be potent inhibitors of P45017alpha.

Correlation between neurotransmitters and neurosteroids and premenstrual syndrome patients of Gan-yang ascending syndrome and Gan-qi stagnation syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the pathogenesis of premenstrual syndrome (PMS), and the correlation between anger and depression and PMS of Gan-yang ascending syndrome (GYAS) and Gan-qi stagnation syndrome (GQSS) by detecting the neuro-reproductive hormones of PMS patients of GYAS and GOSS, thus providing theoretical reliance for diagnostic standards for clinical normative PMS.</p><p><b>METHODS</b>Using techniques such as HPLC, HPLC-MC, ELISA, and radioimmunoassay (RIA), levels of serum sex hormones (follicle stimulating hormone, luteinizing hormone, estradiol, progesterone, testosterone, and prolactin), plasma neurotransmitters (gamma-aminobutyric acid, beta-endorphin, glutamic acid, dopamine, 5-HT, adrenaline, and noradrenaline), neurosteroids (allopregnanolone, pregnenolone, and dehydroepiandrosterone) in the follicular phase and the luteal phase of PMS patients of GYAS (30 cases) and GQSS (30 cases) were detected, and compared with the healthy control group (30 cases).</p><p><b>RESULTS</b>There was no statistical difference in either index of the follicular phase among the 3 groups. Compared with the healthy control group, the testosterone level in PMS patients of GYAS in the luteal phase showed increasing tendency (P > 0.05). The levels of dopamine and 5-HT of PMS patients of GYAS in the luteal phase were higher and the gamma-aminobutyric acid level was lower than those of the healthy control group (all P < 0.05). The levels of adrenaline and noradrenaline of PMS patients of GYAS and GQSS in the luteal phase were higher than those of the healthy control group (all P < 0.05). The levels of allopregnanolone and pregnenolone of PMS patients of GYAS and GQSS in the luteal phase were lower, and the dehydroepiandrosterone level was higher than those of the healthy control group (all P < 0.05). The ratios of dehydroepiandrosterone/allopregnanolone and dehydroepiandrosterone/pregnenolone of PMS patients of GYAS and GQSS in the luteal phase were higher than those of the healthy control group (P < 0.05).</p><p><b>CONCLUSION</b>The decreased levels of pregnenolone and allopregnanolone, increased dehydroepiandrosterone levels, and increased ratios of dehydroepiandrosterone/allopregnanolone and dehydroepiandrosterone/pregnenolone might be one of biological factors for anger and depression in PMS patients of GYAS and GQSS.</p>

Role of Sigma Receptor and Neurosteroids in Pain Sensation / 한양의대학술지

The sigma-1 receptor has recently been implicated in a myriad of cellular functions and biological processes. Previous studies have demonstrated that the spinal sigma-1 receptor plays a pro-nociceptive role in acute pain and that the direct activation of sigma-1 receptor enhances the nociceptive response to peripheral stimuli, which is closely associated with calcium-dependent second messenger cascades including protein kinase C (PKC). In addition, the activation of sigma-1 receptor increases PKC- and protein kinase alpha (PKA)-dependent phosphorylation of the N-Methyl- D-aspartate (NMDA) receptor in the spinal cord, which results in the potentiation of intrathecal NMDA-evoked spontaneous pain behavior. Moreover, the blockade of spinal sigma-1 receptor suppresses the development of neuropathic pain and blocks the increase of phosphorylation of extracellular signal-regulated kinase (ERK) as well as pNR1 in the spinal cord. Recently, it was also reported that spinal neurosteroids such as pregnenolone and dehydroepiandrosterone sulfate, which are recognized as endogenous ligands for sigma-1 receptor, could produce mechanical hypersensitivity via sigma-1 receptor-mediated increase of pNR1. Collectively, these findings demonstrate that the activation of spinal sigma-1 receptor or the increase of neurosteroids is closely associated with the acute pain sensation or the development of chronic pain, and imply that sigma-1 receptor can be a new potential target for the development of analgesics.

Influence of epipregnanolone on the modulation of rapid tolerance to ethanol by neurosteroids

OBJECTIVE: The objective of the present study was to investigate the effect of epipregnanolone on the influence of neurosteroids on the development of rapid tolerance to the motor impairing and hypothermic effects of ethanol. METHOD: Experiment 1: on Day 1 groups of mice were pretreated with saline or with epipregnanolone. After 30 min each group was further divided in subgroups that received ethanol or saline. Thirty, 60 and 90 min after the injections the animals were tested on the rota-rod or the body temperature was measured. On Day 2 all groups received ethanol and a similar procedure was followed to evaluate rapid tolerance. Experiment 2 and 3: On Day 1 groups of mice were treated with epipregnanolone and after 15 min each group was divided into three groups in order to receive pregnenolone sulfate, dehydroepiandrosterone sulfate or saline. Thirty minutes later, each group was further divided into two subgroups in order to receive ethanol or saline, respectively, and 30, 60 and 90 min later the animals were tested as in the experiment 1. On Day 2 all groups received ethanol and a similar procedure was followed to evaluate rapid tolerance. RESULTS: Pretreatment with epipregnanolone (0.10-0.30 mg/kg) significantly blocked the development of tolerance to the motor impairing and hypothermic effects induced by ethanol in mice. Considering tolerance to ethanol-induced motor impairment, epipregnanolone (0.15 mg/kg) reversed the stimulatory action of dehydroepiandrosterone sulfate (0.15 mg/kg), but did not affect the actions of pregnenolone sulfate (0.08 mg/kg). Moreover, epipregnanolone prevented the inhibitory action of allotetrahydrodeoxycorticosterone (0.10 mg/kg). In relation to ethanol-induced hypothermia, the results showed that pretreatment with epipregnanolone (0.30 mg/kg) significantly prevented the stimulatory action of dehydroepiandrosterone sulfate and pregnenolone sulfate, as well as the inhibitory action of...

OBJETIVO: O objetivo do presente estudo foi o de investigar o efeito da epipregnanolona sobre a influência de neuroesteróides no desenvolvimento da tolerância rápida aos efeitos de incoordenação motora e hipotermia induzidos pelo etanol. MÉTODO: Experimento 1: no Dia 1, grupos de camundongos foram pré-tratados com salina ou com epipregnanolona. Após 30 min, cada grupo foi subdividido recebendo etanol ou salina. Aos 30, 60 e 90 min após as injeções, os animais foram testados no rota-rod ou a temperatura corporal foi avaliada. No Dia 2, todos os grupos receberam etanol e um procedimento similar foi seguido para avaliar a tolerância rápida. O pré-tratamento com a epipregnanolona (0,10-0,30 mg/kg) bloqueou significantemente o desenvolvimento da tolerância aos efeitos de incoordenação motora e hipotermia induzidos pelo etanol em camundongos. Experimento 2 e 3: no Dia 1, grupos de animais foram tratados com epipregnanolona e, após 15 min, cada grupo foi dividido em três grupos para receber sulfato de pregnanolona, sulfato de dehidroepiandrosterona ou salina. Após 30 min, cada grupo foi dividido em dois subgrupos para receber etanol ou salina, respectivamente, e após 30, 60 e 90 min os animais foram testados como no experimento 1. No Dia 2, todos os grupos receberam etanol e 30 min após foram testados como mencionado no experimento 1. RESULTADOS: Considerando a tolerância ao prejuízo motor induzido pelo etanol, a epipregnanolona (0,15 mg/kg) bloqueou a ação estimulatória do sulfato de dehidroepiandrosterona (0,15 mg/kg), mas não afetou a ação do sulfato de pregnanolona (0,08 mg/kg). Entretanto, a epipregnanolona bloqueou a ação inibitória da alotetrahidrodeoxicorticosterona (0,10 mg/kg). Em relação à hipotermia induzida pelo etanol, os resultados demonstraram que o pré-tratamento com epipregnanolona (0,30 mg/kg) bloqueou significantemente a ação estimulatória do sulfato de dehidroepiandrosterona e do sulfato de pregnanolona, bem como a ação...

Studies on chemical constituents of rhizomes of Ligusticum chuanxiong / 中国中药杂志

<p><b>OBJECTIVE</b>To study chemical constitutents of the rhizomes of Ligusticum chuanxiong.</p><p><b>METHOD</b>The rhizomes of L. chuanxiong were extracted with water to afford a water extract which was participated between H2O and EtOAc, n-BuOH, successively. The compounds were isolatedand purified by column chromatography from the EtOAc fraction, and identified based on spectral analyses.</p><p><b>RESULT</b>Eleven compounds were isolated from the rhizomes of L. chuanxiong, and structures were characterized as (4S)-p-menth-1-ene4, 7-diol (1), aromadendrane-4alpha, 10beta-diol (2), aromadendrane-4beta, 10alpha-diol (3), aromadendrane-4beta, 10beta-diol (4), augustic acid (5), xiongterpene (6), pregnenolone (7), 3(R), 8(S), 9(Z)-falcarindiol (8), senkyunolide F (9), senkyunolide I (10), 4-hydroxyl-3-butylphthalide (11).</p><p><b>CONCLUSION</b>Compounds 1-5 were obtained from the rhizomes of L. chuanxiong for the first time.</p>

Effect of isopregnanolone on rapid tolerance to the anxiolytic effect of ethanol / Influência da isopregnenolona na tolerância rápida ao efeito ansiolítico do etanol

OBJETIVE: It has been shown that neurosteroids can either block or stimulate the development of chronic and rapid tolerance to the incoordination and hypothermia caused by ethanol consumption. The aim of the present study was to investigate the influence of isopregnanolone on the development of rapid tolerance to the anxiolytic effect of ethanol in mice. METHOD: Male Swiss mice were pretreated with isopregnanolone (0.05, 0.10 or 0.20 mg/kg) 30 min before administration of ethanol (1.5 g/kg). Twenty-four hours later, all animals we tested using the plus-maze apparatus. The first experiment defined the doses of ethanol that did or did not induce rapid tolerance to the anxiolytic effect of ethanol. In the second, the influence of pretreatment of mice with isopregnanolone (0.05, 0.10 or 0.20 mg/kg) on rapid tolerance to ethanol (1.5 g/kg) was studied. CONCLUSIONS: The results show that pretreatment with isopregnanolone interfered with the development of rapid tolerance to the anxiolytic effect of ethanol.

OBJETIVO: Estudos prévios têm mostrado que os neuroesteróides podem bloquear ou estimular o desenvolvimento da tolerância rápida e crônica aos efeitos de incoordenação e hipotermia produzidos pelo etanol. O objetivo do presente estudo foi investigar a influência da isopregnenolona sobre o desenvolvimento da tolerância rápida ao efeito ansiolítico do etanol em camundongos. MÉTODO: Camundongos suíços, machos, foram pré-tratados com isopregnenolona (0,05, 0,10 ou 0,20 mg/kg) 30 minutos antes da administração de etanol (1,5 g/kg). Após 24 horas, todos os animais foram testados no labirinto em cruz elevado. O primeiro experimento foi realizado com o intuito de selecionar uma dose de etanol que produzisse tolerância rápida ao efeito ansiolítico do etanol. No segundo experimento, o objetivo foi investigar o efeito da isopregnenolona (ISO; 0,05, 0,10 ou 0,20 mg/kg) sobre a tolerância rápida ao etanol (1,5 g/kg). CONCLUSÕES: Os resultados mostram que o tratamento prévio com isopregnenolona interferiu no desenvolvimento da tolerância rápida ao efeito ansiolítico etanol.

Determination of unconjugated neurosteroids in rat brain regions by liquid chromatography-negative atmospheric pressure ionization mass spectrometry / 药学学报

<p><b>AIM</b>To simultaneously determine three unconjugated neurosteroids, dehydroepiandrosterone (DHEA) , pregnenolone (PREG), allopregnenolone (AP), from several brain regions of the rat.</p><p><b>METHODS</b>Neurosteroids were isolated separately in a two steps procedure by using ethyl acetate-n-hexane (90:10) as the first step to extract the unconjugated steroids, then the steroid fractions were further purified by SPE. All steroids were derivatized with 2-nitro-4-trifluoromethylphenylhydrazine (2-NFPH) and analyzed by HPLC-MS ( APCI) using selected-ion monitoring. Methyltestosterone was chosen as the internal standard. Results The linear calibration curve of DHEA was obtained in the concentration range of 0.030-2.00 microg x L(-1). The linear calibration curves of PREG and AP were obtained in the concentration range of 0.025-2.00 microg x L(-1). The concentrations of DHEA, PREG and AP in male rat brain regions were (0.70 +/- 0.23), (4.8 +/- 1.9), (1.1 +/- 0.6) ng x g(-1) for frontal cortex, (0.57 +/- 0.28), (6 +/- 3), (0.5 +/- 0.3) ng x g(-1) for hippocampus, (1.5 +/- 1.0), (9 +/- 5), (1.4 +/- 0.9) ng x g(-1) for amygdale, (0.52 +/- 0.14), (7.7 +/- 2.8), (0.5 +/- 0.6) ng x g(-1) for striatum, (2.9 +/- 1.6), (18 +/- 9), (1.6 +/- 1.3) ng x g(-1) for nucleus accumbens, (4.0 +/- 2.0), (27 +/- 12), (0.8 +/- 0.5) ng x g(-1) for pituitary gland, (1.7 +/- 1.2), ( 16 +/- 10), and (0. 8 +/- 0.7) ng x g(-1) for hypothalamus, respectively.</p><p><b>CONCLUSION</b>Good linearity and accuracy were observed for each steroid. The procedure was suitable for measuring concentrations of the unconjugated steroids in rat brain simultaneously.</p>

Dehydropregnenolon acetat synthesized from 3 beta-acetoxy-pregn-5-en-17 beta-OL-20-YN

Researching synthetic method of Dehydropregnenolon acetat (DPA, 3β-acetoxy-pregn-5, 16-dien-20-on) from 3β- acetoxy-pregn-5-en 17β-ol-20-yn, a conclusion is given that using this method dicobalt hexacarbonyl was created in the first time in group acethylen, 3β- acetoxy-pregn-5-en 17β-ol-20-yn is synthesized with good output from equivalent 17β- hydroxy derivative. Respond not attach generates auxiliary products like known methods. Through two methods hydrating and hydrating in gentle conditions, dehydro pregnenolon acetat is synthesized with quite good output from 3β- acetoxy-pregn-5-en 17β-ol-20-yn. Intermediary compounds and final products characterized by melt point, infared spectrum, proton magnetic spectrum and weight spectrum

Effects of morphine dependence on the levels of neurosteroids in rat brain / 药学学报

<p><b>AIM</b>To establish the rat model of morphine-induced conditioned place preference (CPP) and to investigate the effects of morphine psychical dependence on the levels of neurosteroids in rat brain.</p><p><b>METHODS</b>Rats were ip administered morphine 5 mg x kg(-1) for 10 days to induce CPP in morphine group. The concentrations of dehydroepiandrosterone (DHEA), pregnenolone (PREG), allopregnanolone (AP), dehydroepiandrosterone sulfate (DS) and pregnenolone sulfate (PS) in nucleus accumbens (Nac), hypothalamus (Ht), amygdale (A) and plasma of rats were determined with liquid chromatography-negative atmospheric pressure ionization mass spectrometry (LC-MS).</p><p><b>RESULTS</b>Trained with morphine for 10 days resulted in the acquisition of CPP in morphine group with the time that the rats spent in drug-pairing room was longer than that of control group. Compared with control group, morphine treatment could significantly decrease the contents of DHEA in Nac and plasma, decrease that of PREG in Ht.</p><p><b>CONCLUSION</b>Morphine could induce the CPP in rats and affected the contents of some neurosteroids in rat brain, which suggests that endogenous neurosteroids might he related to the development of morphine dependence.</p>

Controle de dopagem de anabolizantes: o perfil esteroidal e suas regulações / Control of doping with anabolic agents: the steroid profile and its regulations

O conceito de perfil esteroidal é discutido neste artigo. As principais vias biossintéticas säo apresentadas. A importância do monitoramento do perfil esteroidal é demonstrada dentro da clínica médica e da medicina esportiva. Parâmetros da literatura para a identificaçäo de dopagem por esteróides endógenos säo apresentados, assim como os fatores que acarretam alterações no perfil esteroidal normal. É dada atençäo especial a essa última abordagem

Expression of 3b-Hydroxysteroid dehydrogenase and P450 side chain cleavage enzyme in the human uterine endometrium

The enzyme complex 3b-hydroxysteroid dehydrogenase/delta(5)-delta(4)-isomerase (3beta-HSD) is involved in the biosynthesis of all classes of active steroids. The expression of 3beta-HSD in human uterine endometrium during the menstrual cycle and decidua was examined in an effort to understand its role during ova implantation. 3beta-HSD was weakly expressed in the glandular epithelium of the proliferative phase and moderately expressed in the glandular epithelium of secretory phase of the endometrium. In the decidua of the ectopic pregnancy, 3beta-HSD was strongly expressed. The human uterine endometrial 3beta-HSD was identified as being the same type as the placental 3beta-HSD by RT-PCR and sequence analysis. In addition to the expression of 3beta-HSD, P450scc was expressed in the decidua of the ectopic pregnancy. These results suggest that pregnenolone might be synthesized from cholesterol by P450scc de novo and then, it is converted to progesterone by 3beta-HSD in the uterine endometrium. The data implies that the endometrial 3beta-HSD can use not only the out-coming pregnenolone from the adrenal gland but also the self- made pregnenolone to produce progesterone. The de novo synthesis of progesterone in the endometrium might be a crucial factor for implantation and maintenance of pregnancy.

Metabolismo energético y esteroidogénico de la plancenta humana / Energetic and steroidogenic metabolism at the human placenta

Las células del sinciciotrofoblasto obtienen el ATP a través de la glucólisis anaerobia. Sin embargo, aunque las mitocondrias de la placenta sintetizan ATP, éste no participa en los procesos citoplasmáticos. Nuestros datos muestran la presencia de una ATP-difosfohidrolsa (apirasa) asociada a las mitocondrias de la placenta, que se inhibe por vanadato y FSBA. En este trabajo proponemos la hipótesis de que la apirasa y el ATP que sintetizan las mitocondrias de las células del sinciciotrofoblasto están asociados al transporte de colesterol necesario para la síntesis de progesterona, y que el uso del ATP y la actividad de la apirasa están asociados a los puntos de unión mitocondriales.

Detection of the Steroidogenic Acute Regulatory(StAR) Protein in Human Testicular Tissue / 대한비뇨기과학회지

PURPOSE: A crucial event in the acute regulation of steroidogenesis by tropic hormone is the delivery of cholesterol from cytosol into the mitochondrial inner membrane where it is converted to pregnenolone by the cytochrome P45O cholesterol side chain cleavage enzyme. Recently, it has been observed that the acute production of steroid hormone depends on a rapidly synthesized, cycloheximide sensitive and highly labile protein that appeared in response to tropic hormone. This protein was named as Steroidogenic Acute Regulatory(StAR) protein. The purpose of this experiment was to detect the StAR protein in human testicular tissue. MATERIALS AND METHODS: Human testicular tissues were obtained during the surgery in patients with cryptorchidism, infertility, and prostate cancer Northern blotting hyridization and RT-PCR were performed to detect the StAR mRNA in human testicular tissues. In addition, immunohistochemical staining was performed to test the presence of the StAR protein in human testicular tissues. RESULTS: The StAR mRNA was detected as a weak band in prostate cancer and infertility patients, but not detected in cryptorchidism patients by Northern blotting hybridization. In RT-PCR of human testicular tissues for StAR mRNA, RT-PCR products(about 2000p) were shown to have in cryptorchidism, infertility, and prostate cancer patients. In immunohistochemical staining of human StAR protein, immunoreactivity of human StAR protein was positive in the interstitial tissues of human testis. CONCLUSIONS: The StAR protein that plays a key role in the steroidogenesis was detected in human testicular tissues and this protein will be effective in pathogenesis and treatment of the diseases that are associated with steroid hormones.

The Molecular Genetic Study Using Automatic Sequence Analyzer on the Steroidogenic Acute Relulatory Protein(StAR) Gene / 대한소아내분비학회지

PURPOSE:The lesion of Congenital Lipoid Adrenal Hyperplasia has been suggested to be in the 1st step of steroidogenesis of conversion of cholesterol to pregnenolone by P450scc. In 1995, however, the molecular defect of this disease has been located in the transport of cholesterol into mitochondria due to defective regulatory protein called Steroidogenic Acute Regulatory Protein(StAR), while the enzyme P450scc itself is normal. This genetic study using automatic sequence analyzer aimed at elucidating the molecular defect in the StAR gene of the two patients. METHODS:This study was performed on the two patients of Congenital Lipoid Adrenal Hyperplasia. Both children were phenotypically females. However, one turned out to have a karyotype of 46, XY, the other 46, XX. Genomic DNAs were extracted from their peripheral blood. We amplified the last exon, hot spot, of the StAR gene using 1 set of primer, S4, 5'-CCT GGC AGC CTG TTT GTG ATA G-3' AS4, 5'-CCT CAT GTC ATA GCT AAT CAG TG-3'. Subsequently, one PCR product have been directly sequenced by dideoxy termination method, and also the other products(patient's and her father's) have been sequenced by automatic sequence analyzer. RESULTS:The mutation was identified in the last exon of the StAR gene, substituting T for A at codon 258, replacing glutamine by stop codon in the two unrelated Korean patients with congenital lipoid adrenal hyperplasia. One patient were found to be homozygote, but the other to be heterozygote for the mutation. CONCLUSIONS:These results indicate that Korean children with congenital lipoid adrenal hyperplasia may be genetically identical as in Japanese. But, we discovered that the hot spot, codon 258, are not always homozygote. We want to emphasize the different point, and to say that we did experiece the automatic sequence analyzer successfully.

Clinical use of Urinary Androgen Metabolites in Hyperprolactinemia / 대한내분비학회지

BACKGROUND: Hyperprolactinemia has been linked with hyperandrogenism and hirsutism in some women. High plasma Dihydroandrosterone and DHA-S levels were reported in patients with hyperprolactinemia and a dissociation of adrenal androgen and cortisol secretion occurs in normal subjects. The mechanism has not been elucidated, but it has been suggested that pituitary factors other than ACTH modulate adrenal androgen synthesis, One candidate hormone is prolactin. Adrenal tissue has been found to possess prolactin receptors and prolactin has been shown to act synergistically with ACTH and lowers the activity of the enzyme 5a-reductase or 3B-hydroxysteroid dehydrogenase (3B-HSD). The aim of this study was to investigate the secretion of adrenal androgen metabolites in patients with idiopathic hyperprolactinemia and prolactinoma and to deterrnine the relationship with prolactin and androgens. METHODS: We measured 24 hour-urinary DHEA, androstenedione, androsterone, pregnenolone, tetrahydrocorticoid and cortisol in 16 normal controls and 5 patients with idiopathic hyperprolac-tinemia (HP) and 12 patients with prolactonoma in the early follicular phase. RESULTS: Urinary DHEA, AD (androsteredione), and androsterone, the metabolites of adrenal androgen, were significantly higher in both patients with idiopathic HP and prolactinoma compared with those in normal controls (p<0.05), whereas they were not different in both disease groups. Urinary pregnenolone levels, early metabolite of adrenal steroid synthesis, were lower in patients. In contrast, urinary tetrahydorcortisol and cortisol were higher in patients compared to controls. There was no difference in DHEA:androsterone ratio between patients and controls. And there were no correlation between prolactin levels and the levels of androgenic metabolites or clinical symptoms. CONCLUSION: Prolactin has a tropic effct on the secretion of androgens and steroids by the adrenal cortex. But prolactin levels were not correlated with androgen levels or clinical symptoms (amenorrhea), and it might have little effect on lowering the activity of 3B-HSD.

A Case of Congenital Lipoid Adrenal Hyperplasia

Congenital lipoid adrenal hyperplasia is the most severe form of CAH, leading to impaired production of all steroid hormones including glucocorticoids, mineralocorticoid, and sex steroids. The affected individuals are all phenotypically female with a severe salt-losing syndrome that is fatal if steroid replacement is not begun immediately after birth. The lesion of this disorder has been suggested to be in the first step of steroidogenesis of conversion of cholesterol to pregnenolone by P450scc. Recently, molecular defect of this disease has been located in the transport of cholesterol into mitochondria due to defective regulatory protein called 'steroidogenic acute regulatory protein' while the enzyme P450scc itself is normal, differing from other types of congenital adrenal hyperplasia. We experienced 2 1/2 month old phenotypical girl who was admitted due to lethargic state and persistent vomiting with severe hyperkemia and hyponatremia. Blood levels of cortisol, aldosteron, and 17-OH progesteron were low and levels of ACTH, angiotensin, and plasma renin activity were high, urinary levels of 17-KS and 17-OHCH were low. The patient was found to have karyotype of 46, XY and has been being treated with predinisolone, fluorocortisol and sodium supplement in diet and doing well. The molecular study for P450scc gene and StAR gene of patient and family is in progress.

A Case of 17a-Hydroxylase Deficiency in 17-Year-Old Girl / 대한내분비학회지

The single enzyme P-450c17 hydroxylase catalyzes the 17a-hydroxylation of both pregnenolone and progesterone and the side-chain cleavage of 17a-hydroxypregnenolone and 17a-hydroxypro- gesterone to dehydroepiandrosterone and androstenedione. This enzyme is located in the endoplasmic reticulum and consists of a P-450c17 and a specific flavoprotein NADPH-cytochrome P-450 reductase. The clinical picture and hormonal pattern in 17a-hydroxylase deficiency have been consistent in both genotypic sexes with hypergonadotropic hypogonadism in whom the virtual absence of gonadal steroids results in a female phenotype with primary amenorrhea and pseudohermaphro- ditism in the male and underdeveloped secondary sex characteristics and hypermineralocorticoidism with hypertension, hypokalemia, suppressed renin-angiotensin system and extremely reduced aldo-sterone production. A 17-year-old girl visited endocrine clinic because of amenorrhea, absence of pubic and axillary hair, and hypertension. she had elevated levels of serum corticosterone, deoxycorticosterone(DOC), 18-hydroxycorticosterone(18-OHB). Stumulation with ACTH effected minimal increase in the elevated steroids and the ACTH-stimulated 18-OHB to aldosterone ratio was more than 280. These hormonal patterns appear to be homozygote in 17a-hydroxylase deficiency.

A Case of Congenital Lipoid Adrenal Hyperplasia

Congenital lipoid adrenal hyperplasia is the rarest type among salt losing types of congenital adrenal hyperplasia. The defect of this disorder is in the cholesterol side chain cleavage enzyme(P450SCC)which converts cholesterol to pregnenolone. W experienced a case of 20,22 desmolse deficiency in a 21-day old phenotypically female who was admitted to our hospital due to lethargy and dark skin pigmentation. The characteristic findings were decreased serum cortisol, aldosterone, testosterone, increased ACTH. The ACTH and hCG stimulation test were performed and there were no response. The sex chromosomal analysis showed made XY. One year later after hormone therapy, growth and development are normal.