Refractory Hypertension and Isosexual Pseudoprecocious Puberty Associated with Renin-Secreting Ovarian Steroid Cell Tumor in a Girl

Steroid cell tumor, not otherwise specified (NOS), are rare ovarian tumor, in addition, it is more rare in children. The majority of these tumors produce several steroid hormones, particularly testosterone. Estrogen also secreted by steroid cell tumor, NOS, but it is uncommon. Furthermore, hypertension is an infrequent sign in steroid cell tumor, NOS. An 8.5-yr-old girl with hypertension and frequent vaginal spotting visited at our clinic. On laboratory evaluation, secondary hypertension due to an elevated plasma renin level and isosexual pseudoprecocious puberty was diagnosed. Right solid ovarian mass was detected in radiologic tests. She underwent a right ooporectomy and it revealed renin and progesterone receptor positive steroid cell tumor, NOS. After operation, her blood pressure returned to normal level and vaginal bleeding disappeared. Even though this case is very rare, when hypertension coincides with virilization or feminization, a renin-secreting ovarian steroid cell tumor, NOS, should be considered.

Letter to the Editor: Hypotension after Etomidate Use in Sepsis

No abstract available.

Effects of soluble antigen-induced immune cell activation on steroidogenesis in murine lymphoid organ.

The effect of soluble antigenic (bovine serum albumin, BSA) stimulation to induce steroidogenesis in murine lymphoid organs with concomitant changes in proinflammatory or inflammatory cytokine levels and its implication in the alteration of T-cell response was studied in the mice. Male Swiss albino mice (6-8 weeks old) with average body weight (20 +/- 4 g) were randomly assigned to 3 groups and injected with BSA in presence and absence of Freund's complete or incomplete adjuvant, whereas the control group received only saline. After 3 weeks, animals were sacrificed, and serums as well as lymphoid organs were collected. From the lymphoid tissue homogenate, the activities of steroidogenic enzymes and corticosterone and cytokine levels of the serum were estimated. Steroidogenic enzyme activities in murine lymphoid organs, as well as the pro-inflammatory and inflammatory cytokines levels in serum increased after Freund's complete adjuvant-emulsified BSA administration, as compared to control. The serum corticosterone and serum cytokine profile were also elevated. Results suggested that soluble protein antigen (BSA) administration stimulated steroidogenesis in murine lymphoid tissues and rise in the pro-inflammatory or inflammatory cytokine levels might indicate monocyte recruitment as well as TH1 activation.

Pharmacological management of Cushing's syndrome: an update

The treatment of choice for Cushing's syndrome remains surgical. The role for medical therapy is twofold. Firstly it is used to control hypercortisolaemia prior to surgery to optimize patient's preoperative state and secondly, it is used where surgery has failed and radiotherapy has not taken effect. The main drugs used inhibit steroidogenesis and include metyrapone, ketoconazole, and mitotane. Drugs targeting the hypothalamic-pituitary axis have been investigated but their roles in clinical practice remain limited although PPAR-gamma agonist and somatostatin analogue som-230 (pasireotide) need further investigation. The only drug acting at the periphery targeting the glucocorticoid receptor remains Mifepristone (RU486). The management of Cushing syndrome may well involve combination therapy acting at different pathways of hypercortisolaemia but monitoring of therapy will remain a challenge.

O tratamento de escolha para a síndrome de Cushing ainda é a cirurgia. O papel da terapia medicamentosa é duplo: ele é usado para controlar o hipercortisolismo antes da cirurgia e otimizar o estado pré-operatório do paciente e, adicionalmente, quando ocorre falha cirúrgica e a radioterapia ainda não se mostrou efetiva. Os principais medicamentos são empregados para inibir a esteroidogênese e incluem: metirapona, cetoconazol e mitotano. Medicamentos visando o eixo hipotálamo-hipofisário têm sido investigados, mas seu papel na prática clínica permanece limitado, embora o agonista PPAR-gama e análogo de somatostatina, som-230 (pasireotídeo), requeira estudos adicionais. A única droga que age perifericamente no receptor glicocorticóide é a mifepristona (RU486). O manejo da síndrome de Cushing deve envolver uma combinação terapêutica atuando em diferentes vias da hipercortisolemia, mas o monitoramento dessa terapia ainda permanece um desafio.

Effect of simultaneous exposure to lead and cadmium on gonadotropin binding and steroidogenesis on granulosa cells: an in vitro study.

Effects of lead (Pb) and cadmium (Cd) both alone or in combination on the binding of LH and FSH on isolated granulosa cells were studied. Granulosa cells isolated from proestrous rats were incubated (in vitro) with lead acetate and/or cadmium acetate (0.03 microM of Pb or Cd) for 1 hr. LH binding was dropped to 84% in Pb treated cells, 72.5% in Cd treated cells and 74.8% in combined metal treated cells compared to control. FSH binding dropped to 85.5% in Pb treated cells, 71.16% in Cd treated cells and 72.5% in combined metal treated cells compared to control. Activity of 17beta Hydroxy Steroid Dehydrogenase (17betaHSDH), a key steroidogenic enzyme was reduced by 52% in Cd and 37% in combined metal exposed cells whereas Pb exposed cells showed 31% reduction in the enzyme activity. Pretreatment with SH groups protectants (glutathione [GSH], dithiothretol [DTT]) and zinc caused an ameriolation in enzyme activity whereas Zn pretreatment showed an increase in gonadotropin binding in metal exposed cells. These results suggest that both Pb and Cd can cause a reduction in LH and FSH binding, which significantly alters steroid production in vitro and exerts a direct influence on granulosa cell function.

Anti-steroidogenic activity of floral extract of Thespesia populnea Corr. in mouse ovary.

Anti-steroidogenic activity of various extracts of T. populnea was screened in female albino mice. The weight of the uterus and ovaries were reduced significantly and the cholesterol and ascorbic acid content in ovaries were significantly elevated due to the treatment with extract of T. populnea. The significant inhibition of delta 5, 3 beta hydroxy steroid dehydrogenase and glucose-6-phosphate dehydrogenase, the two key enzymes involved in ovarian steroidogenesis were also observed in mouse ovaries after 15 days of treatment.

Gentamicin induced inhibition of steroidogenic enzymes in rat testis.

Gentamicin is an aminoglycoside antibiotic, widely used for treating many gram negative bacterial infections. Though nephrotoxicity is the most highlighted side effect, it has also been found to cause an alteration in the phosphatase activities of testes and accessory sex organs and a decline in the sperm count. This study was designed to assess the effects of gentamicin on testicular steroidogenesis and to ascertain whether such alterations are reversible. Laboratory inbred adult, male, 'Wistar' strain rats were chosen as the experimental animal. A significant dose-dependant reduction in the activities of the two steroidogenic enzymes, accompanied with a significant decrease in ascorbic acid and elevation of level of cholesterol was observed. The effects were maximum at a dose of 100 mg/kg, b.wt. After 15 days of withdrawal of the drug therapy the biochemical parameters namely ascorbic acid and cholesterol returned to normal levels whereas the activities of the two dehydrogenases showed a compensatory increase. This indicates that gentamicin affects the steroidogenic enzymes, causing an alteration in the formation of testosterone, which was manifested in the elevated cholesterol in the adult rat testes. However, these alterations were reversible.

Effect of insulin-like growth factor-1 on steroidogenesis in cultured carp ovarian follicles: interactions with estradiol.

The biological action of insulin like growth factor-1 (IGF-1) on follicular steroidogenesis during follicular development in common carp was examined. Studies were carried out by culturing small (1-2 mm diam.) and large (> 2 mm diam.) follicles. IGF-1 (0.3-100 ng/ml) had no effect on progesterone accumulation or aromatase activity during 48 hr culture of small follicles. Progesterone accumulation by large follicles was also unaffected by IGF-1 over the same period, although aromatase activity was stimulated in a dose dependent manner (8-fold increase over basal levels with a maximum stimulatory dose of 30 ng IGF-1/ml). In contrast, small and large follicles responded to IGF-1 in terms of both progesterone accumulation and aromatase activity after longer periods of culture (4 days for progesterone and 6 days for aromatase). Concurrent treatment of small follicles with estradiol (10(-7) M) enhanced the action of IGF-1 on both indices of steroidogenesis and advanced the time at which IGF-1 stimulated activity was first detectable. The effect of estradiol on follicular IGF-1 responsiveness were independent of cell number. In summary, these results demonstrate varied actions of IGF-1 carp ovarian follicular steroidogenesis in vitro. The results indicate that carp follicles acquire responsiveness to IGF-1 in terms of aromatase activity during follicular development in vivo and that estradiol can induce the response in vitro. The results also suggest that estrogen and progesterone biosynthesis by cultured carp ovarian follicles is differentially regulated by IGF-1. Together, these results provide new insights into the biological actions of IGF-1 in fish ovary.

Regulacion de la esteroidogenesis testicular por oxido nitrico / Regulation of testicular steroidogenesis by nitric oxide

Los macrófagos testiculares y las células endoteliales, constituyen una fuente parácrina potencial de óxido nítrico (NO) en el testículo. En este trabajo, se investigó el efecto de liberadores de NO sobre la esteroidogénesis en una línea celular tumoral de Leydig murina y en células de Leydig de rata. Se observó que los liberadores de NO inhiben, de una manera reversible, la esteroidogénesis inducida por hCG en ambos tipos celulares. También se estudió el mecanismo de acción del NO. Contrariamente a lo observado en otros sistemas, los efectos inhibitorios del NO sobre la esteroidogénesis en células de Leydig no son mediados por GMPc, puesto que el NO no aumenta la producción de GMPc ni los análogos de GMPc reproducen los efectos del NO. El NO tampoco modifica la producción de AMPc, el segundo mensajero de la acción gonadotrófica. Cuando se evaluó el efecto del NO sobre el camino esteroidogénico en las células MA10, se encontró que el NO inhibe la conversión de colesterol a pregnenolona. En conjunto, estos resultados muestran un efecto inhibitorio de liberadores de NO sobre la esteroidogénesis en células de Leydig y sugieren que el NO puede inhibir en forma directa la enzima que escinde la cadena lateral del colesterol (citocromo P-450scc) como lo hace con otras hemo proteínas que incluyen diferentes citocromos P-450.

Patterns of long-term steroidogenesis stimulation by ACTH and phorbol ester

Adrenocorticotropic hormone (ACTH) triggers well-defined responses in Y-1 cells. Among them is steroidogenesis stimulation. We have previously shown that phorbol 12-myristate 13-acetate (PMA), an activator of the calcium- and phospholipid-dependent protein kinase (PKC) is able to mimic all the responses triggered by ACTH in these cells, including steroidogenesis stimulation. Short (2 h) treatment with PMA leads to only 20-30 per cent of the maximal steroidogenesis stimulation obtained with ACTH. However, the steroid secretion in the 2 h that follows the short-term (2 h) PMA treatment reaches the same levels as observed with ACTH, i.e., a 12- to 15-fold increase. We also show that this effect is restricted to cells treated with PMA for up to 4 h, while treatment for longer periods of time causes a reduction of the steroid biosynthesis rate, an effect that is not observed in cells treated with ACTH or N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (dcAMP). These results suggest that activation of PKC can elicit the first phase of ACTH steroidogenesis stimulation, but not the second one, which strictly depends on activation of cAMP-dependent protein kinase.

The rat thymus contains a heparin-binding factor that modulates steroidogenesis in the testis

Thymus development and function are under the influence of hormones secreted by the gonads and pituitary. On the other hand, thymurus is crucial for the development of reproductive capacitities in female and male rats and we have shown that a factor derived from the prepubertal rat thy mus has antigonadotropic effect in ovarian and testis cells in vitro. In the present paper we show that the rat thymic factor which modulates gonadotropin action in the gonads is an heparin-binding factor. This capacity was also used as a useful tool to obtain this activity from semipure extracts. An acetone extract was prepared from 15 day old male rats and subjected to molecular filtration chromatography. The activity, of those fractions was investigated in a testis cells biossay, by measuring testosterone secretion under basal and hCG-stimulation. Active fraction were processed in a heparin-Sepharose affinity column. We found that fractions that eluted with 0.6 and 2M NaCl/10mM Tris had biological specific activity. The electrophoretic procedure showed that the apparent molecular weight of the Heparin Sephadex binding factor is 60 kDa. Since this factor was obtained from a protein peak that eluted in the volume of carbonic anhidrase a dimerization process could be involved. Present results show that the rat thymus has an heparin-binding factor that interacts with hCG in testis cells. This factor could play an interesting role in the mutual influence between thymus and gonads.

El papel de los esteroides en el desarrollo folicular del mamífero / Steroids role in mammal follicular growth

El propósito de esta revisión es conocer la regulación del desarrollo folicular, la ovulación y del cuerpo lúteo por medio de la síntesis de esteroides en el folículo. La esteroidogénesis ovárica y el desarrollo folicular junto con los mecanismo de control neuroendocrino involucrados en la secreción de gonadotropinas actúan para producir una serie de eventos endocrinológicos y morfológicos que tienen como finalidad la producción de un ovocito completamente maduro y capaz de ser fecundado

Spermatogenic and steroidogenic impairment after chromium treatment in rats.

Feeding of hexavalent chromium at doses of 20, 40 and 60 mg/kg daily for 90 days caused cellular impairment in rat testis. Spermatogenic inhibition coupled with deminution in testicular protein, DNA and RNA was significant at the doses 40 and 60 mg kg chromium. Decline of Leydig cell population and nuclear diameter indicated the steroidogenic impairment and the effect was confirmed by the significant inhibition of 3 beta-delta 5-hydroxy steroid dehydrogenase along with low level of serum testosterone.

The effect of serum on in vitro maturation, in vitro fertilization and steroidogenesis of bovine oocytes co-cultured with granulosa cells

The influence of fetal calf serum alone (fcs) or associated with proestrous (FCS + PCS), ESTROUS (FCS + ECS) or metaestrous (FCS + MCS) cow serum added to the culture medium and of the steroids produced by co-cultured granulosa cells were evaluated in terms of the in vitro maturation (IVM) and fertilization (IVF) of bovine oocytes. Supplementation of the medium with 9FCS + ECS and FCS + MCS resulted in higher proportions of oocytes that reached metaphase II (96.0 per cent and 93.3 per cent, respectively) and in higher proportion of embryos that reached the four- and eight-cell/morula stages (51.9 per cent and 65.6 per cent, respectively), whereas the supplementation with FCS and FCS + pcs resulted in only 79.2 per cent and 67.5 per cent, respectively, of matured oocytes nd 26.7 per cent and 34.4 per cent, respectively, of cleaved embryos. These findings show that the best IVM and IVF were obtained at lower concentrations of estradiol produced by co-cultured granulosa cells (supplementation with FCS + ECS: 10.3 ng/ml and FCS + MCS: 2.1 ng/ml), whereas the worst results in IVM and IVF occurred at higher concentrations of estradiol that were obtained with FCS (33.1 ng/ml) and FCS + PCS (19.9 ng/ml) supplementation. These data suggest an inhibitory effect of estradiol on resumption of oocyte meiosis in vitro

Mitomycin C induced inhibition of adrenal steroidogenesis in female rats.

Mitomycin C (MC), an antibiotic which depresses DNA synthesis causes suppression of enzyme delta 5 3 beta-hydroxysteroid dehydrogenase (delta 5 3 beta OHD) and glucose-6 phosphate dehydrogenase (G-6 PD) in the rat adrenal tissue. The treatment resulted in a fall in DNA content together with an accumulation of cholesterol and ascorbic acid in the gland. The results suggest a diminution in adrenal steroid biogenesis similar to gonadal inhibition previously reported.

Pathology of ovary, uterus, vagina and gonadotrophs of female mice fed on Zn-deficient diet.

Dietary Zn-deficiency in mature female mice for 6 weeks caused a retardation of ovarian growth characterized by lack of vesicular and Grafian follicles, degenerated corpus luteum, distorted cell membranes of granulosa cells with pycnotic nuclei, poor development of theca interna, inordinate accumulation of sudanophilic granules in theca interna and interstitial cells. The vagina and uterus did not exhibit cyclic changes in their cytoarchitecture as a result of the cessation of estrous cycle after 6 weeks of dietary treatment. They displayed wide spread degenerative changes in their myometrial and endometrial layers. The uterine glands appeared collapsed with little or no secretion. The vagina lacked cornification. Their gonadotrophs reacted positive to PAS, identical to the control group observed at diestrous stage. However, they did not display a negative reaction, characteristic of the gonadotrophs at estrous stage of the control group, examined even at an interval of 1 day for 6 days in succession. These results point towards the suspension of steroidogenesis inspite of intact gonadotrophs under Zn-deficiency condition.