Interleukin-1 alpha modulates luteinizing hormone stimulated cyclic AMP and progesterone release from human granulosa cells in vitro.

This study examines the possible direct effect of interleukin-1 alpha (IL-1 alpha) upon human granulosa cells. The cells were isolated from follicles of stimulated cycles in women undergoing oocyte retrieval for in-vitro fertilization. Purified cell preparations were cultured for different time periods in the presence of IL-1 alpha and human luteinizing hormone (LH) or follicle stimulating hormone. IL-1 alpha stimulated basal as well as LH-induced progesterone accumulation. The response in terms of cyclic AMP was more complex, there was no effect of IL-1 alpha on basal cyclic AMP accumulation. However, at the highest concentration tested (50 IU/ml), IL-1 alpha enhanced cyclic AMP accumulation over that seen with LH alone. At a lower concentration, IL-1 alpha either had no effect or was slightly inhibitory to the LH-induced cyclic AMP accumulation, depending on the culture period. Our results, taken together with other findings, are compatible with the view that IL-1 alpha has a potential regulatory role in the granulosa-luteal cell transition in the human ovary.     

Preincubation of human granulosa cells with gonadotrophin prevents the cloprostenol-induced inhibition of progesterone production.

Human granulosa cells, from women undergoing ovum collection for in-vitro fertilization (IVF), will luteinize in vitro and provide a model for investigating the antigonadotrophic action of a prostaglandin F2 alpha (PGF2 alpha) analogue, cloprostenol, on granulosa-derived luteal cells. The granulosa cells were cultured in a defined medium and exposed to treatments during a preincubation period of 0 to 3 days and a final incubation with low density lipoprotein (LDL) from days 3 to 4. In the absence of human chorionic gonadotrophin (HCG), progesterone production was low, whereas exposure to HCG in the final incubation resulted in a 10-fold increase in progesterone concentrations. The inclusion of cloprostenol with HCG in the final incubation significantly (P less than 0.05) inhibited HCG-stimulated progesterone production. Exposure to HCG during the preincubation prevented the antigonadotrophic action of cloprostenol in the final incubation. The antigonadotrophic action of cloprostenol was retained when the granulosa cells were exposed to cloprostenol during the preincubation. Omission of LDL from the final incubation lowered the production of progesterone but the pattern of responses to HCG and cloprostenol were similar. Prevention of the antigonadotrophic action of cloprostenol after exposure to HCG may be a mechanism through which chorionic gonadotrophin can prevent regression of the corpus luteum in early pregnancy. Cloprostenol does not appear to inhibit LDL-stimulated steroidogenesis in human granulosa cells.     

Progesterone Receptor-Containing Neurons in the Guinea-Pig Mediobasal Hypothalamus have Axonal Projections to the Medial Preoptic Area

The location and number of progesterone receptor-containing neurons in the mediobasal hypothalamus that project to the medial preoptic area were determined by combining retrograde fluorescent tract tracing with progesterone receptor immunocytochemistry. Injections of the retrograde tract tracer Fluoro-gold were made in the preoptic area of female guinea-pigs ovariectomized and primed with estradiol. After 5 days survival to allow for retrograde transport, tissue sections were incubated with monoclonal antibodies to the progesterone receptor to detect the presence of progesterone receptor-immunoreactive neurons. Cell bodies were labelled with Fluoro-gold throughout the arcuate nucleus. These neurons were not concentrated in any particular area of the nucleus but were diffusely distributed bilaterally. Retrogradely-labelled neurons were also observed in the ventrolateral and ventromedial nuclei mainly contralateral to the injection site. Progesterone receptor immunofluorescence labelled a subpopulation (7% to 10%) of these retrogradely-labelled cells particularly in the arcuate nucleus, including the median eminence. The double-labelled cells were more numerous in the anterior two-thirds of the arcuate nucleus. Although our estimates of the proportion of hypothalamic progesterone receptor-immunoreactive neurons that sent axons directly to the medial preoptic area were low, (about 0.35%), these neurons may be part of a neural circuit involved in the regulation of reproductive processes.     

Hormone receptors and obesity in Japanese women with breast cancer

Summary An association between hormone receptors in primary breast cancer and obesity determined prior to mastectomy was investigated in 128 Japanese women. The following criteria for obesity were used: (1) weight 60 kg (132 lbs), (2) weight kg/height cm–105 1.3, (3) weight lbs/height in 2.30, (4) body surface area 1.56 m². In view of the 4 criteria, tumor estrogen receptor (ER) values 4 fmol/mg were observed in obese patients more often than in nonobese patients, though the difference was not statistically significant. The same tendency was observed in the postmenopausal subgroup, 62 patients, especially in the 36 patients more than 5 years beyond menopause. However, there was still no statistical difference between obese and nonobese patients because the number of subjects was small. The same tendency was observed in the case of progesterone receptor (PgR) (6 fmol/mg) as observed in the case of ER. Address for reprints: Dr. Keijiro Kuno, Department of Surgery, Cancer Institute Hospital, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo, Japan 170     

Regional and selective effects of oestradiol and progesterone on NMDA and AMPA receptors in the rat brain

We investigated the effect of 10 months ovariectomy and a correction therapy, 2 weeks before the rats were killed, of oestradiol, progesterone or their combination on NMDA and AMPA receptor binding in the hippocampus, dentate gyrus, striatum, nucleus accumbens and frontal cortex of the rat brain as well as on amino acid levels in frontal cortex. NMDA and AMPA binding densities were assayed by autoradiography using, respectively, L-[3H]glutamate and [3H]AMPA; amino acid concentrations were measured by high performance liquid chromatograhy (HPLC) coupled with UV detection. Ovariectomy was without effect on NMDA and AMPA binding density in all brain regions assayed except in the hippocampal CA1 region and dentate gyrus where it decreased NMDA binding density compared to intact rats values. Oestradiol restored and increased NMDA binding density in the CA1 subfield and the dentate gyrus of ovariectomized rats but, by contrast, it decreased binding density in the striatum and in the frontal cortex while having no effect in the CA2/3 subfield of the hippocampus and in the nucleus accumbens. Oestradiol was without effect on AMPA binding density in the hippocampus and the dentate gyrus but it reduced AMPA binding density in the striatum, the frontal cortex and the nucleus accumbens. Progesterone, and oestradiol combined with progesterone, decreased NMDA but not AMPA binding density in the frontal cortex of ovariectomized rats, and they were without effect on these receptors in the other brain regions assayed. Amino acid concentrations in the frontal cortex were unchanged after ovariectomy or steroid treatments. The effect of oestradiol in the hippocampus confirmed in the present study and our novel findings in the frontal cortex, striatum and nucleus accumbens may have functional significance for schizophrenia and neurodegenerative diseases.     

胃癌的雌孕激素受体检测及应用三苯氧胺治疗的研究

目的　探讨胃癌的雌激素受体 (ER)、孕激素受体 (PR)表达情况及其对预后的影响 ,观察三苯氧胺 (TAM)在胃癌治疗中的作用。方法　从 1993年 2月到 2 0 0 0年 12月 ,用免疫组化SP法 ,对 12 3例胃癌术后标本进行了ER、PR检测 ,并将TAM应用于胃癌的内分泌治疗 ,追踪随访 5年。结果　①胃癌的ER、PR阳性率均为 36 5 9% ( 45 / 12 3) ;②分化好 (高、中分化 )的胃癌ER、PR阳性率18.5 7% ( 13/ 70 ) ,分化差 (低分化腺癌 ,粘液腺癌和印戒细胞癌 )的胃癌ER、PR阳性率 60 38% ( 32 / 5 3) ,统计学处理有显著差异 (P <0 .0 5 ) ;③ER、PR阳性表达与临床分期呈正相关 ,分期越晚阳性率越高 ,但统计学无显著差异 (P >0 .0 5 ) ;④接受化疗 34例 ,化疗同时辅以TAM内分泌治疗 31例 ,5年生存率分别为 2 6.47% ( 9/ 34 )、5 1.61% ( 16/ 31) ,二者有显著差异 (P <0 .0 5 )。结论　本研究表明 ,ER、PR阳性表达的胃癌是一种雌、孕激素依赖性肿瘤 ,化疗联合TAM内分泌治疗 ,可抑制胃癌细胞的生长 ,提高 5年生存率     

Direct gamete uterine transfer in patients with tubal absence or occlusion

Purpose: Our aim was to examine the potential of the uterine cavity to affect fertilization and early embryo development. Design: A prospective IRB-approved protocol for patients fulfilling study eligibility criteria was used. Methods: Patients studied included those with primary or secondary infertility, aged less than 38 years, with no history of severe male-factor infertility, and with hysterosalpingogram-and laparoscopic-confirmed bilateral proximal tubal occlusion. Superovulation induction was accomplished with a combination of GnRH agonist and menotropins, with serum hormonal and sonographic monitoring. Within 24 hr prior to, and again at the time of, ovulatory hCG administration, progesterone (P4) was given. Sonographic-guided transvaginal retrieval was performed 35 hr after hCG. Between four and six oocytes were returned to the uterine cavity, admixed with sperm, immediately following retrieval. Luteal support consisted of daily P4 administration. Results: Of the 20 patients recruited for the study, all completed the retrieval and transfer procedure. A total of four clinical pregnancies was achieved, with one early first-trimester loss, one late first-trimester loss (Trisomy 14), and two healthy term infants delivered. IVF of surplus oocytes demonstrated a 82.5% fertilization rate and 66.7% cleavage following cryopreservation. Conclusions: Human fertilization can be achieved through direct uterine transfer of gametes. Furthermore, administration of P4 prior to the ovulatory dose of hCG is compatible with in vitro or in vivo fertilization and implantation.     

Associations of alcohol, height, and reproductive factors with serum hormone concentrations in postmenopausal Japanese women

We measured serum levels of estradiol (E₂), sex hormone-binding globulin (SHBG), progesterone, and dehydroepiandrosterone sulfate (DHEAS) in 61 postmenopausal women drawn from female residents in a community in Japan to evaluate the relationships between these hormone levels and potential breast cancer risk factors. The information on reproductive history, body size, alcohol use, and physical activity was obtained by means of a self-administered questionnaire. There was a significant trend in increasing E₂ level with increasing height after taking account of age and body mass index (BMI) (p for trend = 0.04). BMI was inversely associated with SHBG level after controlling for age (p for trend = 0.01). Decreasing progesterone with increasing BMI was observed after controlling age and history of hysterectomy (P=0.05). Alcohol consumption was positively associated with E₂ level and there was a strong linear trend after controlling for age, height, and BMI (p for trend=0.001). Trend for increasing DHEAS with alcohol consumption was also statistically significant after controlling for age and history of hysterectomy (p for trend=0.01). Reproductive factors as well as physical activity were not related to any of the hormone levels.     

No association between immunohistochemical expression of p53, c-erbB-2, Ki-67, estrogen and progesterone receptors in female papillary thyroid cancer and ionizing radiation

An association has previously been reported between exposure to medical diagnostic ionizing radiation and papillary thyroid cancer in women. To further evaluate potential mechanisms in carcinogenesis, the expression of p53, c-erbB-2, as well as Ki-67, estrogen and progesterone receptors were analyzed by immunohistochemistry in 19 women exposed to X-rays and for comparison in nine women without such reported exposure. They all had papillary thyroid cancer. No difference was found between these groups. The results of this study showed that p53, c-erbB-2, Ki-67, estrogen and progesterone receptors are not involved in papillary thyroid cancer associated with exposure to medical diagnostic ionizing radiation.