Expression of steroidogenic acute regulatory protein in the human corpus luteum throughout the luteal phase.

The expression of the steroidogenic acute regulatory protein (StAR) in the human corpus luteum (CL) was examined throughout the luteal phase. The primary 1.6-kb StAR transcript was in greater abundance in early (3.1-fold) and mid (2.2-fold) luteal phase CL compared with late luteal phase CL. The larger StAR transcript (4.4 kb) was found in early and midluteal phase CL, but was not detected in late luteal phase specimens. Mature StAR protein (30 kDa) was present in lower amounts within late CL compared with early and midluteal phase CL. The StAR preprotein (37 kDa) was also detected in greater abundance in early and midluteal CL. Immunohistochemistry revealed that StAR staining was most prominent in thecal-lutein cells throughout the luteal phase. The intensity of the signal for StAR exhibited significant changes throughout the luteal phase, being most intense during the midluteal phase and least during the late luteal phase. Plasma progesterone concentrations were highly correlated (r = 0.73 and r = 0.79) with luteal expression of the preprotein and mature StAR isoforms, respectively, throughout the luteal phase. To examine the LH dependency of StAR expression, the GnRH antagonist, Cetrorelix, was administered during the midluteal phase. Cetrorelix caused a decline in serum LH levels within 2 h, which, in turn, caused a pronounced decline in plasma progesterone within 6 h. The StAR 4.4-kb transcript was not detectable, and the 1.6-kb transcript was reduced by approximately 50% within 24 h of Cetrorelix treatment. The mature 30-kDa StAR protein level declined approximately 30% after Cetrorelix treatment. We conclude that 1) StAR mRNA and protein are highly expressed in early and midluteal phase CL; 2) StAR protein is present in both thecal-lutein and granulosa-lutein cells throughout the luteal phase; 3) StAR protein levels in the CL are highly correlated with plasma progesterone levels; 4) declining StAR mRNA and protein levels are characteristic of late luteal phase CL; and 5) suppression of LH levels during the midluteal phase results in a marked decline in plasma progesterone and a diminished abundance of StAR transcripts in the CL without a corresponding significant decline in StAR protein. Collectively, these data are consistent with the idea that StAR gene expression is a key determinant of luteal progesterone during the normal menstrual cycle. However, the pharmacologically induced withdrawal in the midluteal phase of LH support diminishes luteal progesterone output by mechanisms others than reduced StAR protein levels.

Amplification of inflammation in emphysema and its association with latent adenoviral infection.

This study examines the hypothesis that the cigarette smoke-induced inflammatory process is amplified in severe emphysema and explores the association of this response with latent adenoviral infection. Lung tissue from patients with similar smoking histories and either no (n = 7), mild (n = 7), or severe emphysema (n = 7) was obtained by lung resection. Numbers of polymorphonuclear cells (PMN), macrophages, B cells, CD4, CD8 lymphocytes, and eosinophils present in tissue and airspaces and of epithelial cells expressing adenoviral E1A protein were determined using quantitative techniques. Severe emphysema was associated with an absolute increase in the total number of inflammatory cells in the lung tissue and airspaces. The computed tomography (CT) determined extent of lung destruction was related to the number of cells/m(2) surface area by R(2) values that ranged from 0.858 (CD8 cells) to 0.483 (B cells) in the tissue and 0.630 (CD4 cells) to 0.198 (B cells) in the airspaces. These changes were associated with a 5- to 40-fold increase in the number of alveolar epithelial cells expressing adenoviral E1A protein in mild and severe disease, respectively. We conclude that cigarette smoke-induced lung inflammation is amplified in severe emphysema and that latent expression of the adenoviral E1A protein expressed by alveolar epithelial cells influenced this amplification process.

Hormonal profile, endometrial histology and ovarian ultrasound assessment during 1 year of nomegestrol acetate implant (Uniplant).

The present study assesses the endocrinological, endometrial histology and vaginal ultrasound profiles of nomegestrol acetate subdermal implant users at varying times after insertion. Follicle stimulatory hormone, luteinizing hormone, oestradiol, progesterone, vaginal ultrasound assessment of the ovaries and the histological dating of the endometrium were serially assessed for a period of 50 days immediately after the insertion, and after at 6 months and 12 months of use. The endocrinological results of this prospective observational clinical trial indicated that 75% of the cycles across the study period in Uniplant users were anovulatory, 63% showing development of a persistent non-luteinized follicle. Anovulatory cycles devoid of follicular development were seen primarily in the first months after Uniplant insertion. Ovulatory cycles represented 25% of the Uniplant cycles. Inadequate luteal phase or disregulation of follicular growth was a common feature of ovulatory cycles. In conclusion, these findings suggest that the contraceptive mechanisms of a single nomegestrol acetate subdermal implant involve prevention of follicular growth, development of a persistent non-luteinized follicle, inadequate luteal phase and disruption of the endometrial architecture.

Localization of insulin-like growth factor (IGF-I) and IGF-I receptor expression in human corpora lutea: role on estradiol secretion.

OBJECTIVE: To determine whether insulin-like growth factor (IGF-I) and its receptors are expressed by human corpus luteum (CL) and to establish the effect of IGF-I on E2 biosynthesis in human luteal cell cultures. DESIGN: Middle corpora lutea were obtained from women undergoing surgical sterilization. The tissue was frozen for binding and in situ studies or dispersed for cell cultures. SETTING: Procedures were performed at the San Borja-Arriarán Hospital, National Health Service, and Institute of Maternal and Child Research, Faculty of Medicine, University of Chile. PATIENTS: Twelve patients aged 30 to 40 years requesting surgical sterilization in our institution. The laparotomy was scheduled 6 to 8 days after ovulation. MAIN OUTCOME MEASURES: Expression of IGF-I and IGF-I receptor messenger RNAs (mRNAs) by in situ hybridization. Concentration of IGF-I receptor and binding characteristics. Production of E2 by luteal cells. RESULTS: The binding of IGF-I was detected in middle human CL membranes. In addition, this tissue expressed the mRNAs of IGF-I and its receptor. In culture, IGF-I caused a progressive increase on E2 production. CONCLUSION: These data suggest that the IGF-I system is present in middle human CL. The topographic distribution of IGF-I and its receptors and the ability of IGF-I to stimulate E2 secretion strongly suggest that IGF-I has a role as a paracrine or autocrine regulator of the human luteal function.

Cistitis hemorrágica masiva por ciclofosfamida y su tratamiento con formalina: experiencia en niños / Massive hemorrhagic cystitis due to ciclosphosphamide and its treatment with formalin: experience in children

En los últimos diez años, tres niños con cuadros oncológicos en tratamiento quimioterápico, que incluía ciclosfosfamida, presentaron hematuria masiva con anemia severa, resistente a tratamiento generales y locales, su gravedad llegó a plantear la cistectomía radical. La instilación intravesical de formalina al 2 por ciento detuvo las hemorragias

Steroidogenic capacity and oxidative stress-related parameters in human luteal cell regression.

The steroidogenic capacity and oxidative stress-related parameters of the human corpus luteum (CL) at different stages of the luteal phase were studied under basal and human chorionic gonadotropin (hCG)-stimulated conditions. Mid CL exhibited the maximal steroidogenic capacity, together with lower levels of glutathione and higher thiobarbituric acid reactants content, macrophage count, and superoxide dismutase (SOD) activity, compared to the late CL. Addition of hCG to luteal cell cultures led to a preferential increase in progesterone synthesis in the late CL compared to the mid CL, without changes in the oxidative stress-related parameters, except for the increased SOD activity found in the late CL. It is concluded that an oxidative stress condition is established in the mid CL, coinciding with the maximal steroidogenic capacity and macrophage infiltration of the organ, which may be of relevance as one of the major mechanisms initiating CL involution in the human.

Morpho-functional study of human luteal cell subpopulations.

It has been reported that the mammalian corpus luteum is composed mainly of two subpopulations of luteal cells (large and small) of different morphology and function. The aims of this study were first to characterize cytologically the human corpus luteum throughout the luteal phase, and second to establish the in-vitro steroidogenic capacity of a well-defined human mid-luteal cell system. The results show that the most predominant (> 70%) cell shape, is polyhedric, and the number of cells per unit area is significantly different in the early, mid- and late corpus luteum (P < 0.005). Moreover, small cells (< 22 microns) were most common (56.8%) in all tissues analysed. On the other hand, both subpopulations synthesized progesterone, oestradiol and testosterone, although a significantly greater production of basal steroids was observed in large luteal cells (P < 0.05). Nevertheless, the response of small cells to human chorionic gonadotrophin (HCG) was significantly greater (P < 0.05) than that of large cells, in agreement with the preferential specific binding obtained for [125I]HCG to the small cell subpopulation. In summary, these results indicate that the human corpus luteum possesses distinct cell types, which may be related to endocrine function and its control.