Adrenal insufficiency is a contraindication for omalizumab therapy in mast cell activation disease: risk for serum sickness.

Omalizumab is an effective therapeutic humanized murine IgE antibody in many cases of primary systemic mast cell activation disease (MCAD). The present study should enable the clinician to recognize when treatment of MCAD with omalizumab is contraindicated because of the potential risk of severe serum sickness and to report our successful therapeutic strategy for such adverse event (AE). Our clinical observations, a review of the literature including the event reports in the FDA AE Reporting System, the European Medicines Agency Eudra-Vigilance databases (preferred search terms: omalizumab, Xolair®, and serum sickness) and information from the manufacturer's Novartis database were used. Omalizumab therapy may be more likely to cause serum sickness than previously thought. In patients with regular adrenal function, serum sickness can occur after 3 to 10 days which resolves after the antigen and circulating immune complexes are cleared. If the symptoms do not resolve within a week, injection of 20 to 40 mg of prednisolone on two consecutive days could be given. However, in MCAD patients whose adrenal cortical function is completely suppressed by exogenous glucocorticoid therapy, there is a high risk that serum sickness will be masked by the MCAD and evolve in a severe form with pronounced damage of organs and tissues, potentially leading to death. Therefore, before the application of the first omalizumab dose, it is important to ensure that the function of the adrenal cortex is not significantly limited so that any occurring type III allergy can be self-limiting.

Triamcinolone and ritonavir leading to drug-induced Cushing syndrome and adrenal suppression: description of a new case and review of the literature.

The protease inhibitor (PI) ritonavir is a potent inhibitor of cytochrome P450 (CYP) 3A4 activity and frequently prescribed to boost the effectiveness of other PIs as part of highly active antiretroviral therapy. It is well established that ritonavir is capable of inducing iatrogenic Cushing syndrome (ICS) through a drug-drug interaction with inhaled fluticasone that leads to the inhibition of CYP3A activity. A rapidly increasing number of case reports are being published describing ICS induced by the interaction of ritonavir and injected corticosteroids, namely triamcinolone acetonide. A review of the current literature identified 15 cases (including the one reported here) of ICS and suppression of the hypothalamic-pituitary-adrenal axis after periradicular injection of triamcinolone acetonide. Considering an aging human immunodeficiency virus (HIV)-infected population an increasing number of patients will present with degenerative musculoskeletal disease and be seeking pain relief. Based on data reported in the literature and our own experience triamcinolone injections during ritonavir-based therapy should be avoided. After failure of all conservative therapeutic options methylprednisolone may represent a therapeutic alternative for steroid injections in HIV patients receiving PI-based antiviral therapy since it has to date not been associated with ICS.

Noradrenergic-glucocorticoid modulation of emotional memory encoding in the human hippocampus.

BACKGROUND: Current rodent models emphasize the joint action of the stress mediators noradrenaline (NE) and cortisol (CORT) in conferring a memory advantage of emotional over neutral stimuli. METHOD: Using a pharmacological strategy of tackling this stress-related mechanism to enhance human episodic (autobiographical) memory, we measured amygdala-hippocampal responses during encoding of emotional and neutral stimuli with functional magnetic resonance imaging in 51 healthy subjects under four pharmacological conditions in a double-blind parallel group design: (i) placebo; (ii) the NE-reuptake inhibitor reboxetine (4 mg); (iii) hydrocortisone (synthetic CORT) (30 mg); or (iv) both agents in combination. RESULTS: Differential drug effects were found in the left hippocampus, whereas hydrocortisone alone selectively decreased hippocampal responses to emotional relative to neutral stimuli, reboxetine potentiated hippocampal responses to these stimuli. Importantly, the inhibitory influence of hydrocortisone was reversed by co-administration of reboxetine. CONCLUSIONS: Our results imply that stress levels of CORT alone attenuate hippocampal responses to emotional stimuli, an effect possibly related to a regulatory negative feedback loop. However, when simultaneously elevated to stress levels, NE and CORT act together to synergistically enhance hippocampal activity during encoding of emotional stimuli, a mechanism that may turn maladaptive under circumstances of traumatic stress.

High-risk pregnancy management in women with hypopituitarism.

Pregnancy after complete loss of pituitary function is uncommon. However, advances in fertility treatment have led to increased pregnancy rates in hypopituitary women. We hereby present a literature review of pregnancies affected by hypopituitarism, including a comparison with published controls; further, we add one case report of severe hypopituitarism where third-trimester oxytocin supplementation was performed. As only limited information is available on management and outcome, our purpose was to determine obstetric complications associated with deficiency of pituitary hormones. The analysis of 31 pregnancies in 27 women revealed that hypopituitary women are at increased risk: postpartum hemorrhage occurred in 8.7%, transverse lie in 16%; 42.4% of the newborns were small for gestational age. These findings are supposedly the result of uterine dysfunction caused by hormone deficiency. Oxytocin supplementation was performed with the aim to establish physiologic conditions and to prevent postpartum uterine inertia. In this case substitution may have contributed to correct fetal presentation but did not prevent postpartum hemorrhage. Further investigations into both oxytocin-dependent and -independent mechanisms regulating uterine contractions and contractility are necessary to develop strategies for prevention of uterine inertia in oxytocin-deficient pregnancies.

[Which antiepileptic drug for men with epilepsy? A critical epileptological and andrological review]. / Welches Antiepileptikum für den Mann? Kritische Beurteilung aktueller Kenntnisse aus epileptologischer und andrologischer Sicht.

BACKGROUND: Choice of antiepileptic drugs (AED) in the treatment of epilepsy is partly based on the assessment of drug-induced sexual dysfunction in men. We examined current knowledge on the effect of AED on reproductive functions in men with epilepsy. METHODS: Original publications and review articles were evaluated by an epileptologist and a specialist in andrology. RESULTS: Only few data are available to assess the effects of AED (i.e. carbamazepine, oxcarbazepine, valproate, and lamotrigine) on male sexual function. Moreover, the effect of epilepsy itself is almost never considered. Temporal lobe epilepsy may however influence the release of sexual steroid hormones, resulting in reduced serum concentrations of testosterone. Enzyme-inducing AED increase the amount of testosterone bound to the sexual hormone-binding globulin (SHBG). However a correlation to sexual functions is not well established. In addition, AED may affect spermatogenesis and sperm motility, possibly resulting in infertility. CONCLUSIONS: Based on current data, lamotrigine and valproate are the AED of choice. These AED have little or no effect, respectively, on SHBG and exert no negative effects on sexual steroid hormones in men.

Peri-operative glucocorticoid replacement therapy in transsphenoidal pituitary adenoma surgery: a prospective controlled study.

BACKGROUND: We set out to prospectively study the peri-operative changes of the hypothalamic-pituitary-adrenal axis (HPA), and to test the hypothesis that the peri-operative corticoid replacement regimen used at the authors' institution in patients with impaired HPA undergoing transsphenoidal pituitary adenoma surgery is adequate. METHOD: Thirty seven patients (21 females, 16 males, mean age 50.6 years) underwent transsphenoidal pituitary adenoma surgery (mean tumour diameter 20.6 mm, 13 tumours hormone-secreting). The HPA functions of these patients were classified as impaired (group A, n = 15) or preserved (group B, n = 22) according to the results of a pre-operative corticotrophin releasing-hormone test (CRHT). Eleven patients (9 female, 2 male, mean age 53.6 years) without pituitary adenomas and with a preserved HPA (as assessed by medical history and morning serum cortisol (MSC) measurements), undergoing decompressive surgery for degenerative lumbar disc disease, were also studied (group C). On the day of surgery, the patients of group A received 100 mg hydrocortisone (HC) replacement therapy, which was thereafter gradually tapered off in a standardised fashion. The patients of groups B and C were not treated with corticoids. Pre-operative, intra-operative and post-operative variables of these three patient groups were compared. FINDINGS: The urinary free cortisol excretion (UFC) in group A declined from 6732 +/- 7683 microg/d on the day of surgery to 305 +/- 358 microg/d on the 10(th) post-operative day. In group B, the respective UFC values were 12,851 +/- 16,278 microg/d and 223 +/- 235 microg/d. In both of these groups, the mean UFC did not fall into the normal range during the first ten post-operative days. On none of the post-operative days, was there a significant difference between the UFC of groups A and B. The UFC values of group C dropped from 177 +/- 157 microg/d on the day of surgery to 87 +/- 61 microg/d on post-operative day six, reaching the normal range from the 2(nd) post-operative day onwards. All UFC values of group C were significantly lower than those of group A and B. None of the evaluated clinical, laboratory and MRI parameters, as disclosed by uni- and multivariate analysis, showed any significant influence on the peri-operative UFC values. CONCLUSIONS: The peri-operative UFC of pituitary adenoma patients with preserved HPA was very high, as compared to patients with degenerative lumbar disc disease. The present study showed for the first time, that the proposed regimen of peri-operative corticoid replacement therapy used in patients with pituitary adenomas and impaired HPA raised cortisol levels to match the physiological increase of UFC in patients with pituitary adenoma surgery and preserved HPA. However, although statistically not significant, the UFC of patients with pituitary adenomas and preserved HPA seemed considerably higher on the day of surgery than in patients with pituitary adenomas and HPA impairment. Although there is no evidence to make it mandatory, administration of 150 mg instead of 100 mg HC substitution on the day of pituitary adenoma surgery in patients with HPA impairment may be prudent.

Delayed postoperative hyponatremia followed by acute renal failure in a patient with an ACTH-secreting microadenoma of the pituitary.

The selective transsphenoidal adenomectomy of an ACTH-secreting microadenoma was followed by clinically symptomatic delayed hyponatremia in an otherwise healthy patient. During mild fluid restriction for the treatment of the hyponatremia, acute renal failure occurred. The renal failure was resolved by treatment with furosemide. Fluid restriction is considered a standard therapeutic approach for the treatment of this probably SIADH-induced hyponatremia. Until now, acute renal failure has not been reported under these circumstances. This unique case demonstrates the need of close monitoring of patients with delayed hyponatremia following pituitary surgery.

Diagnostic value of markers M2A, OCT3/4, AP-2gamma, PLAP and c-KIT in the detection of extragonadal seminomas.

AIMS: To compare the suitability of new seminoma markers including transcription factors AP-2gamma, OCT3/4 and M2A for detection of metastatic and extragonadal seminomas with the two well-known markers c-KIT and PLAP. MATERIALS AND METHODS: The immunohistochemical distribution of PLAP, c-KIT, M2A, AP-2gamma and OCT3/4 was examined in two pineal germinomas, 28 metastatic seminomas and 10 of their testicular primaries. Evaluation of specificity was achieved by additional tissue array studies on 75 malignancies other than germ cell tumours (GCT). Clinical data including serum PLAP were available in 18 patients. RESULTS: Compared with other markers, significantly better staining results were observed with antibodies to M2A and AP-2gamma in all seminomatous GCT. In contrast, the staining pattern with antibodies to c-KIT, PLAP and OCT3/4 was variable or absent. The lowest specificity was obtained with c-KIT, which was expressed in a variety of non-GCT. The only M2A+ mesothelioma expressed no other seminoma markers. No correlation between serum PLAP level and tissue PLAP expression was found. CONCLUSIONS: M2A and AP-2gamma are the most sensitive markers for seminoma metastases or primary extragonadal seminomas. Combination of these markers provides highly specific and clear results for detection of a seminomatous GCT.

Impact of androgenic/antiandrogenic compounds (AAC) on human sex steroid metabolizing key enzymes.

Various pesticides, industrial pollutants and synthetic compounds, to which human populations are exposed, are known or suspected to interfere with endogenous sex hormone functions. Such interference potentially affect the development and expression of the male and female reproductive system or both. Chemicals in this class are thus referred to as endocrine disruptors (ED). This emphazises on the relevance of screening ED for a wide range of sex hormone-mimicking effects. These compounds are believed to exert influence on hormonal actions predominantly by (i) interfering with endogenous steroids in that they functionally interact with plasma membrane-located receptors as well as with nuclear receptors both for estrogens and androgens or (ii) affecting the levels of sex hormones as a result of their impact on steroid metabolizing key enzymes. Essential sex hormone-related enzymes within the endocrine system of humans are aromatase, 5alpha-reductase 2 as well as specific sulfotransferases and sulfatases (so-called phase I and phase II enzymes, respectively). Using suitable human tissues and human cancer cell lines (placenta, prostate, liver and JEG-3, lymph node carcinoma of prostate (LnCaP) cells) we investigated the impact of 10 widely used chemicals suspected of acting as ED with androgenic or antiandrogenic activity (so-called AAC) on the activity of these sex hormone metabolizing key enzymes in humans. In addition, the respective effects of six substances were also studied as positive controls due to their well-known specific hormonal agonistic/antagonistic activities. The aim of this report and subsequent investigations is to improve human health risk assessment for AAC and other ED.

Dose distribution in hydrocortisone replacement therapy has a significant influence on urine free cortisol excretion.

We investigated the influence of dose distribution in hydrocortisone replacement therapy on urine free cortisol excretion. To this end, we measured 24-hour urine free cortisol (24-h UFC) in 13 patients with hypocortisolism. The patients took 25 mg hydrocortisone/day according to the following schedules: either a single 25 mg hydrocortisone dose at 8:00 a.m., or 15 mg hydrocortisone at 8:00 a.m. and 10 mg hydrocortisone at 2:00 p.m., or 5 mg hydrocortisone at 8:00 a.m., 10:00 a.m., 2:00 p.m., 6:00 p.m. and 10:00 p.m. 24-h UFC decreased significantly with increasing division of the daily 25 mg hydrocortisone dose. When taking 25 mg hydrocortisone in a single morning dose, the mean 24-h UFC was 649 +/- 52 nmol/day (mean +/- SEM). When the daily dose was divided into doses of 15 mg and 10 mg hydrocortisone, 24-h UFC was reduced by 28 % to 466 +/- 39 nmol/day (p < 0.002). After division into five doses of 5 mg, 24-h UFC was reduced by 42.8 % to 371 +/- 36 nmol/day (p < 0.001) compared to the single 25 mg dose. These data demonstrate that consideration of the dose distribution in hydrocortisone replacement therapy when analysing 24-h UFC is of clinical importance.

Growth hormone deficiency in pituitary disease: relationship to depression, apathy and somatic complaints.

OBJECTIVE: Adults with GH deficiency (GHD) have been reported to suffer from increased levels of depression and apathy, which are thought to contribute to the reduced quality of life observed in these patients when compared with healthy controls. Recent studies, however, cast doubt on the attribution of these impairments to GHD as opposed to an unspecific stress response to the chronic medical condition. DESIGN: To further clarify this relationship, we used psychometric tests to quantify depression, apathy and typical psychosomatic complaints in patients with different types of pituitary disease and compared the results with measurements of the patients' widely varying GH status. SUBJECTS AND METHODS: In 98 patients, serum IGF-I was measured and at least one provocative test of the somatotrope pituitary axis was performed (GH-releasing hormone test (GHRHT) and/or insulin tolerance test (ITT)). All patients completed a set of well-established psychometric instruments (Beck Depression Inventory (BDI), Apathy Evaluation Scale (AS) and List of Somatic Complaints (LSC)). In addition, AS was administered in an informant report version for completion by a close relative or friend to verify the validity of the patient's self assessment. RESULTS: No relationship between measures of GHD (IGF-I, GHRHT and ITT) and psychometrically measured depression, apathy or psychosomatic well-being was found. A highly significant linear correlation between scores of all psychometric instruments (BDI, AS and LSC) was found. CONCLUSIONS: The absence of any relationship between the severity of GHD and the level of depression/apathy/psychosomatic complaints suggests that these impairments are not specific symptoms of GHD. The reported improvement of these symptoms under GH substitution therapy might thus be interpreted as a secondary effect of somatic effects of GH substitution. Consequently, indication for GH substitution therapy should not be based on psychological impairments alone without the presence of somatic symptoms of GHD.

Endocrinological outcome following first time transsphenoidal surgery for GH-, ACTH-, and PRL-secreting pituitary adenomas.

BACKGROUND: To study remission rates and pituitary functions following transsphenoidal surgery of newly diagnosed GH-, ACTH-, and PRL-secreting pituitary adenomas. METHODS: Out of a series of 329 newly diagnosed pituitary adenomas, 131 (39.8%) were hormone (67 GH-, 27 ACTH-, 37 PRL-) secreting. PRL-secreting adenomas were subjected to surgery because they failed to respond to previous medical treatment therapy. The data on secreting adenomas, regarding the results of standardised endocrinological testing, MRI findings and water metabolism disturbances, were extracted retrospectively from the pituitary data-base of the hospital. The mean follow-up was 3.7 years. RESULTS: The overall remission rate for PRL-secreting adenomas (27%) was significantly lower than for GH- (71.6%) and ACTH-secreting (81.5%) ones. Remission rates correlated negatively with the magnitude of preoperative hormone excess (not in Cushing's disease), tumour size (not in prolactinoma) and invasiveness. Generally, the improvement of the adenopituitary functions was statistically significant during the first three postoperative months, and thereafter remained unchanged. Diabetes insipidus persisting for more than three months occurred with similar frequency in the three patient groups (in 9.4% of GH-, in 6.7% of ACTH-, and in 10% of PRL-secreting adenomas). Tumour regrowth occurred more often in PRL-(20%) than in ACTH- (9.1%) and GH- (0%) secreting tumours. CONCLUSIONS: In GH- and ACTH-secreting pituitary adenomas, remission rates were significantly higher and recurrence rates lower than in PRL-secreting adenomas, which had failed to respond to previous medical therapy. The overall postoperative adenopituitary function was improved in all patient groups. Diabetes insipidus occurred with similar frequency in all patient groups. When reporting on results of surgery for secreting pituitary adenomas, not only remission and recurrence rates, but also the results of the pituitary function should be included.

Typical ocular findings in a patient with multiple endocrine neoplasia type 2b syndrome.

BACKGROUND: Multiple endocrine neoplasia (MEN) type 2b syndrome is accompanied by typical ocular findings; however, the disease is often only diagnosed at an advanced stage by symptoms of C-cell carcinoma or pheochromocytoma and is then fatal in most cases. Therefore, the importance of ophthalmic assessment in making the diagnosis has to be stressed. METHODS: The history and ocular findings of a patient with MEN 2b syndrome are described, and a brief overview of the syndrome is given. RESULTS: Slit-lamp examination showed extremely thickened corneal nerves as well as multiple small plexiform and nodular subconjunctival tumors. Both eyes also displayed thickened upper and lower eyelids. A molecular genetic study of the RET proto-oncogene showed a heterozygous ATG to ACG mutation in codon 918 of exon 16. CONCLUSION: Greatly thickened corneal nerves and subconjunctival tumors may be the first hint of MEN 2b. Whenever greatly thickened corneal nerves are detected, MEN 2b must be ruled out.

Inhibition of human cytochrome P450 aromatase activity by butyltins.

Organotin compounds are widely used as antifouling agents and bioaccumulate in the food chain. Tributyltin chloride (TBT) has been shown to induce imposex in female gastropods. On the basis of this observation it has been suggested that TBT acts as an endocrine disrupter inhibiting the conversion of androgens to estrogens mediated by the aromatase cytochrome P450 enzyme. However, to date, the molecular basis of TBT-induced imposex and in particular its putative inhibitory effects on human aromatase cytochrome P450 activity have not been investigated. Therefore, we examined the effects of the organotin compounds tetrabutyltin (TTBT), TBT, dibutyltin dichloride (DBT) and monobutyltin trichloride (MBT) on human placental aromatase activity. TBT was found to be a partial competitive inhibitor of aromatase activity with an IC(50) value of 6.2 microM with 0.1 microM androstenedione as substrate. TBT impaired the affinity of the aromatase to androstenedione but did not affect electron transfer from NADPH to aromatase via inhibiting the NADPH reductase. DBT acted as a partial but less potent inhibitor of human aromatase activity (65% residual activity), whereas TTBT and MBT had no effect. The residual activity of TBT-saturated aromatase was 37%. In contrast, human 3beta-HSD type I activity was only moderately inhibited by TBT (80% residual activity). Moreover, neither TTBT or DBT nor MBT inhibited the 3beta-HSD type I activity. Together, these results suggest that the environmental pollutants TBT and DBT, both present in marine organisms, textile and plastic products, may have specific impacts on the metabolism of sex hormones in humans.

Characterization of the 5alpha-reductase-3alpha-hydroxysteroid dehydrogenase complex in the human brain.

Although androgen metabolism in the human brain was discovered almost 30 yr ago, conclusive studies on the enzymes involved are still lacking. We therefore investigated 5alpha-reductase and colocalized 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) activity in cerebral neocortex (CX) and subcortical white matter (SC) specimens neurosurgically removed from 44 patients suffering from epilepsy. We could demonstrate the presence of the 5alpha-reductase-3alpha-HSD complex in the biopsies of all patients under investigation. Inhibition experiments with specific inhibitors for 5alpha-reductase type 1 and type 2 revealed strong evidence for the exclusive activity of the type 1 isoform. We detected a significantly higher 5alpha-reductase activity in CX than in SC (P< 0.0001), but no sex-specific differences were observed. Furthermore, we found that, in contrast to liver, only 3alpha-HSD type 2 messenger RNA is expressed in the brain and that its expression is significantly higher in SC than in CX without sex-specific differences. The present study is the first to systematically characterize the 5alpha-reductase-3alpha-HSD complex in the human brain. The lack of sex-specific differences and also the colocalization of both enzymes at all life stages suggest a more general purpose of the complex, e.g. the synthesis of neuroactive steroids or the catabolism of neurotoxic steroids, rather than control of reproductive functions.

The hypothalamic-pituitary-adrenal axis of patients with severe sepsis: altered response to corticotropin-releasing hormone.

OBJECTIVE: To investigate the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis in patients with severe sepsis by stimulating with corticotropin-releasing hormone (CRH). DESIGN: Prospective observational study in consecutive intensive care unit patients with severe sepsis. SETTING: Surgical intensive care unit and outpatient department of endocrinology in a university hospital. PATIENTS: The study included 20 patients with the diagnosis of severe sepsis; six critically ill, nonseptic patients after major surgery; ten patients with primary adrenal insufficiency; ten patients with anterior pituitary insufficiency; and ten individuals without clinical signs of HPA axis disturbance. INTERVENTIONS: CRH tests were performed with an intravenous bolus injection of 100 microg of human CRH. MEASUREMENTS AND MAIN RESULTS: We studied the functional integrity of the HPA axis in patients with severe sepsis by performing the CRH test. In addition, during the period of severe sepsis, we repeatedly measured basal plasma concentrations of adrenocorticotropin hormone (ACTH) and cortisol. The mean basal plasma cortisol concentration was decreased significantly in nonsurvivors with severe sepsis (288.8 +/- 29.1 [sem] nmol/L) compared with survivors (468.1+/- 18.6 nmol/L; p <.01). By calculating the ACTH/cortisol indices, we found no evidence for adrenal insufficiency in patients with severe sepsis. The mean ACTH/cortisol indices of nonsurvivors with severe sepsis (0.02 +/- 0.008) and survivors (0.01 +/- 0.002) were significantly lower compared with the index of patients with primary adrenal insufficiency (6.8 +/- 1.0; p <.001). In contrast, in nonsurvivors with severe sepsis, the plasma cortisol response to CRH stimulation was impaired compared with survivors: The mean basal cortisol concentration within the CRH test was 269.4 +/- 39.8 nmol/L in nonsurvivors compared with 470.8 +/- 48.4 nmol/L in survivors and increased to a peak value of 421.6 +/- 72.6 nmol/L in nonsurvivors and 680.7 +/- 43.8 nmol/L in survivors (p <.02). However, the change in plasma cortisol, expressed as mean +/- sem and calculated by subtracting the basal cortisol from the peak cortisol after CRH stimulation, was not significantly different in survivors with severe sepsis (243.5 +/- 36.1, range 111.0-524.0 nmol/L, n = 15) compared with nonsurvivors (161.0 +/- 38.9, range 42.0-245.0 nmol/L, n = 5; p >.05). CONCLUSIONS: We found lower basal plasma cortisol concentrations in nonsurvivors compared with survivors of severe sepsis. In addition, the plasma cortisol response to a single CRH stimulation was impaired in nonsurvivors compared with survivors. Reduced responses to CRH stimulation may reflect a state of endocrinologic organ dysfunction in severe sepsis.

Expression of the 17beta-hydroxysteroid dehydrogenase type 5 mRNA in the human brain.

An enzyme-mediated metabolism of androgens and estrogens including 17beta-HSD activity in the brain of vertebrates was discovered approximately 30 years ago. Mainly 5alpha-reductase and aromatase have been studied in detail. Recently we could demonstrate reductive and oxidative 17beta-HSD activity as well as considerable mRNA expression of the 17beta-HSD types 3 and 4 in the human brain. In the present study, we report on 17beta-HSD type 5 mRNA expression in brain tissue of women and men. Data analysis did not reveal sex specific differences, but we determined a significantly higher mRNA concentration in the subcortical white matter (SC) than in the cerebral cortex (CX). Investigation of reductive 17beta-HSD in vitro activity with 2 microM androstenedione as the substrate revealed no sex specific differences. Testosterone formation was significantly higher in SC than in CX. Moreover, enzyme activity was significantly higher in brain tissue of adults compared to that of children.

Corticosteroid receptor mRNA expression in the brains of patients with epilepsy.

The effects of corticosteroids in the brain are mediated through the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). We used a sensitive competitive RT-PCR assay to quantify the amounts of GR and MR mRNA in human brain tissue specimens from patients with focal epilepsies. GR and MR mRNAs were expressed at approximately the same levels in the temporal lobe, frontal lobe, and hippocampus as compared to tissues with high glucocorticoid/mineralocorticoid receptor expression (liver/kidney). GR and MR mRNA concentrations in the temporal lobe increased markedly during childhood and reached adult levels at puberty. GR and MR mRNA expression was significantly higher in the temporal lobe and frontal lobe cortex of women than in those of men. In women, MR and GR mRNA concentrations were markedly lower in hippocampal tissue than in frontal and temporal lobe cortex tissue. In conclusion, our data demonstrate sex- and site-dependent expression of corticosteroid receptor mRNA in the human brain.