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1.
O Naess E Haug A Attramadal A Aakvaag V Hansson F French 《Canadian Metallurgical Quarterly》1976,99(5):1295-1303
The cytosol fractions of the anterior pituitary, hypothalamus, preoptic area and brain cortex of androgen "insensitive" (Tfm) rats possess androgen receptors. However, in the Tfm rats the androgen binding per mg protein was only 10-15% of that in the corresponding normal littermates (Nl). The physicochemical properties of the androgen receptors in the anterior pituitary of the Tfm rat were indistinguishable from those of the normal rat. Thus, no distinctive differences were observed with regard to electrophoretic mobility in 3.25% polyacrylamide gels, isoelectric point (pI=5.8), binding affinity (KD=1.5 X 10(-9)M), temperature stability, sulfhydryl dependence and steroid specificity. It is, therefore, likely that the very low androgen binding capacity by the anterior pituitary and the central nervous system is due to an extreme reduction in the receptor number rather than to the presence of abnormal receptors. Since in the Tfm animals the androgen receptor number is reduced by 85-90%, it is to be expected that very high doses of androgens would be required to achieve hormonal effects. In fact, low doses of 5alpha-dihydrotestosterone propionate (50 mug/100 g body weight) given sc daily for 12 days had no effect on serum levels of LH and FSH. However, very high doses (2 mg/100 g body weight) of testosterone propionate and 5alpha-dihydrotestosterone propionate, which maintained circulating androgen levels above 20 ng/ml, significantly reduced serum gonadotropin levels in castrated Tfm rats. In normal littermates both low and high doses of the androgens suppressed gonadotropin secretion to low levels. These findings strongly indicate that androgen receptors are essential to androgen action on the anterior pituitary and central nervous system in the rat. The serum levels of testosterone (7.7+/-0.15 (SE) ng/ml) and 5alpha-dihydrotestosterone (0.37+/-0.06 ng/ml) were significantly higher in intact Tfm rats than in normal littermates (2.6+/-0.03 and less than 0.1 ng/ml, respectively). The failure of the elevated concentrations of serum androgens to reduce the high serum levels of LH and FSH in intact Tfm rats is most likely due to the extreme reduction of the androgen receptor number and the consequent insufficient hypothalamic and/or pituitary response to androgens. 相似文献
2.
W Futterweit 《Canadian Metallurgical Quarterly》1998,27(2):209-226
Physiological principles of the interrelationship of sex hormones and their regulation are the foundation of understanding appropriate treatment of the transsexual patient. While both genetic males and females have estrogens and androgens, the quantitative sex hormone production is genetically predetermined by sex hormone production both in the gonads and via peripheral conversion of hormone precursors to sex steroids. Sex hormones exert a negative feedback on the hypothalamus and pituitary gland whereby gonadotropin-releasing hormone (GnRH), pituitary luteinizing hormone (LH), and follicle-stimulating hormone (FSH) are regulated or suppressed by the endogenous levels of these hormones. Sex hormonal therapy induces attenuated GnRH stimulation of LH and FSH causing a reduction of serum sex hormone levels. It is clear that estrogen as well as androgen therapy have a dual role: (i) induction of feminization or virilization and (ii) suppression of the hypothalamic-pituitary-gonadal axis leading to a reduction of endogenous estradiol or testosterone secretion. Cross-sex hormonal treatment may have substantial medical side effects. The smallest dosage of hormonal therapy compatible with the above clinical aims should be used. 相似文献
3.
FJ Rocha LA Wickham JD Pena J Gao M Ono RW Lambert RS Kelleher DA Sullivan 《Canadian Metallurgical Quarterly》1993,46(6):737-749
Androgens are known to regulate both the structure and function of lacrimal tissue in a variety of species. To explore the endocrine basis for this hormone action, the following study was designed to: (1) determine the cellular distribution of androgen receptors in the lacrimal gland; and (2) examine the influence of gender and the endocrine environment on the glandular content of these binding sites. Lacrimal glands were obtained from intact, castrated, hypophysectomized, diabetic or sham-operated male or female adult rats, mice or hamsters, as well as from orchiectomized rats exposed to placebo compounds or physiological levels of testosterone. The cellular location of androgen receptors was evaluated by utilizing an immunoperoxidase protocol, in which a purified rabbit polyclonal antibody to the rat androgen receptor was used as the first antibody. Our findings with lacrimal glands showed that: (1) androgen receptors are located almost exclusively in nuclei of epithelial cells; (2) the cellular distribution or intranuclear density of these binding sites is far more extensive in glands of males, as compared to females; (3) orchiectomy or hypophysectomy, but not sham-surgery or diabetes, lead to a dramatic reduction in the immunocytochemical expression of androgen receptors; and (4) testosterone administration to orchiectomized rats induces a marked increase in androgen receptor content, relative to that in placebo-exposed glands. Our results also reveal that a 10 kb androgen receptor mRNA exists in the rat lacrimal gland. Overall, these findings demonstrate that gender and the endocrine system may significantly influence the distribution of androgen binding sites in rat lacrimal tissue. Moreover, our results show that androgens up-regulate their own lacrimal gland receptors. 相似文献
4.
Hybrid NZB X NZW or NZB X DBA/2 females have markedly accelerated development of autoimmunity when compared with their respective male littermates. This difference is attributable to the ability of male sex hormones to retard the expression of autoimmunity. In contrast to the sex differences in expression of autoimmunity in F1 mice, parental NZB males and females have only minor differences in disease expression. We have been investigating the basis for the difference in anti-T cell antibody production between NZB and F1 mice. In this study, the appearance of antibodies cytotoxic for T cells (NTA) was studied in NZB and DBA/2 mice and in their F1 hybrids and backcross progeny. A major sex difference in NTA production was observed in the F1 hybrids; females produced more NTA than did males. Castration of males led to a marked increase in NTA production. Furthermore, the NTA production of castrated male and female F1 mice was significantly suppressed by administration of testosterone in Silastic capsules. In contrast to the studies in F1 mice, we found little difference between intact male and female parental NZB mice at any age studied. Furthermore, NZB mice of both sexes who were given androgen-containing capsules at 2 weeks of age failed to demonstrate a decrease in NTA production. This result suggested an androgen insensitivity in NZB mice with regard to NTA production. This insensitivity, which appears to be a recessive trait, may help to explain why NZB mice do not manifest the sex differences in disease expression observed in the F1 hybrids. 相似文献
5.
O Tsutsumi 《Canadian Metallurgical Quarterly》1997,55(11):2876-2881
Sex differentiation may be seen as a sequence of gonadal determination, gonadal differentiation, genital differentiation. Malfunction of this causes abnormal female reproductive function. SRY (sex-determining region Y) has been show to induce testis which is needed to bring about development of the other male sex organs. Absence or point or frame shift mutation in the SRY causes XY females. Secondary sex determination depends on testosterone produced by Leydig cells. Testicular feminization syndrome typically lack the normal androgen receptor protein and therefore, they are distinctly female phenotype. Rokitansky syndrome is a type of aplasia vaginae and is a malformation of the Mullerian duct. They all present primary amenorrhea. Secondary amenorrhea is a common type of abnormal female reproductive function and differential diagnosis depends on hormonal analysis. One of the topics includes polycystic ovarian syndrome which is recently treated by laparoscopic surgery. 相似文献
6.
Localization and sex steroid regulation of androgen receptor gene expression in rhesus monkey uterus
OBJECTIVE: To characterize the cellular sites and hormonal regulation of uterine androgen receptor gene expression in the monkey. METHODS: Ovariectomized rhesus monkeys (five in each group) were treated with placebo (the control group), estradiol (E2), E2 plus progesterone, or E2 plus testosterone by sustained-release pellets administered subcutaneously. After 3 days of treatment, uteri were removed and uterine sections were analyzed by in situ hybridization for androgen receptor messenger RNA (mRNA). RESULTS: Androgen receptor mRNA was detected in endometrial stromal cells and myometrial smooth muscle cells, with lesser expression in endometrial epithelial cells. Both E2 and E2 plus progesterone treatment doubled androgen receptor mRNA levels in stromal cells (P < .01), whereas E2 plus testosterone treatment increased stromal androgen receptor mRNA levels by about five-fold (P < .001) compared with placebo treatment. In the endometrial epithelium, E2 alone did not increase androgen receptor mRNA levels significantly. However, the E2 plus progesterone and E2 plus testosterone treatments increased epithelial androgen receptor mRNA levels by 4.3 and 5 times, respectively (P = .008 and P < .002, respectively). Androgen receptor mRNA was distributed homogeneously in smooth muscle cells across the myometrium. Estradiol treatment alone did not increase myometrial androgen receptor mRNA levels significantly, but the E2 plus progesterone and E2 plus testosterone treatments increased myometrial androgen receptor mRNA levels by 1.8 and 2 times, respectively (P = .001 and P < .001, respectively). CONCLUSION: Androgen receptor gene expression was detected in all uterine cell compartments where it was subject to significant sex steroid regulation. The fact that androgen receptor mRNA levels were consistently up-regulated by a combined E2 plus testosterone treatment while E2 treatment alone had little or no effect shows that a collaborative action of E2 and testosterone enhances androgen receptor expression in the monkey uterus. 相似文献
7.
8.
The basis for the medical treatment of prostate cancer is inhibition of the influence of testosterone on the prostate. Surgical castration is in 1997 still the gold standard; it reduces the testosterone level by 90% and the level of dihydrotestosterone (the active metabolite) by 60%. In the eighties luteinising hormone releasing hormone (LH-RH) analogues were introduced to avoid the psychological burden of castration. After an initial stimulation (the flare-up) testosterone decreases to castrate level within 3 weeks. Recently (non-steroidal) anti-androgens, competitive inhibitors of dihydrotestosterone on receptor level were introduced. There are also drugs which inhibit the conversion of testosterone to dihydrotestosterone: 5 alpha-reductase inhibitors. Non-steroidal anti-androgens and 5 alpha-reductase inhibitors do not decrease the testosterone level and therefore cause less loss of libido and energy than castration. Combination of (chemical) castration and anti-androgens is called maximum androgen blockade. This treatment has limited additional value in proportion to the increase in side effects and costs. A new form of treatment is intermittent androgen blockade. With this strategy growth of hormone-insensitive cells in the prostate, which is considered the main determinant of the poor prognosis, might be delayed with reduction of side effects and costs. The role of imidazoles is still investigated; the role of cytotoxic drugs is mainly palliative. 相似文献
9.
To understand gonadal tumor development, we have previously created a mouse model in which mice deficient in the inhibins develop gonadal sex cord-stromal tumors with essentially 100% penetrance. These tumors develop as early as 4 weeks of age and cause cancer cachexia-like symptoms and subsequent death in the inhibin-deficient mice. Gonadectomized inhibin-deficient mice eventually develop adrenal cortical tumors with nearly 100% penetrance. These studies have identified inhibin as a novel secreted tumor suppressor protein with specificity for the gonads and adrenal glands. Sex steroids have been implicated to influence gonadal tumor development in humans and mice. To determine the role of androgens in gonadal tumorigenesis in inhibin-deficient male mice, we have used a genetic intercross strategy, breeding inhibin alpha mutant mice with tfm (testicular feminization, a naturally occurring androgen receptor mutant) carrying females to eventually generate compound mutant male mice that lack inhibins and carry the tfm mutation. These compound mutant mice, like inhibin-deficient mice, continue to develop testicular tumors and the accompanying cancer cachexia-like wasting syndrome. Consistent with these findings, elevated levels of activins A and B secreted from the gonadal tumors are seen in the adult compound mutant mice as well as the secondary pathological consequences of these high activin levels in the livers and glandular stomachs. However, in contrast to male mice lacking only inhibin, in which essentially 100% of the testicular tumors are hemorrhagic, 65% of the tumors in these compound mutant male mice are less hemorrhagic, and approximately 50% of the compound mutants live longer than 17 weeks of age (95% of the male mice lacking only inhibin die by 12 weeks). These results suggest that androgens are not required for testicular tumor development in inhibin-deficient mice, but may play a regulatory role in testicular tumor progression. 相似文献
10.
The syndrome of androgen insensitivity is a genetically determined illness occurring in subjects with a karyotype 46XY and female or male phenotype. The insensitivity to androgens is caused by the mutations in the androgen receptor gene, comprising 8 exons and localized on chromosome X near the centromere, between Xq13 and Xp11. The androgen receptor belongs to a family of steroid hormone receptors which possess common structural features since it comprises six functional regions (domains) of which the DNA binding domain has a characteristic zinc fingers motif. The lack, deficiency or the disturbance in the function of the receptor, results in a set of clinical symptoms which allow to distinguish four distinct clinical forms of the illness: complete and incomplete testicular feminization syndromes, Reifenstein syndrome and the syndrome of male infertility. In this review data from literature were presented and discussed, regarding the structure and action of the androgen receptor in target cells and the significance of the investigations on the structure-function relationship of this receptor in understanding the pathogenesis of the syndrome of androgen insensitivity was emphasized. 相似文献
11.
GR Hogan 《Canadian Metallurgical Quarterly》1977,3(3):577-588
Lead acetate (PbAc) was tested for its effects on the production and release of erythrocytes-that is, erythropoiesis-in ICR mice. Dose-survival data indicate that a dosage of 20 mg PbAc/100 g body weight represents the maximum tolerable treatment level. No differences in survival at the various levels of the salt were observed with regard to sex or age. For erythropoietic effects of PbAc, mice were injected on day O, and radioiron (59Fe) incorporation percentages were determined at daily intervals through day 8 for both erythrocytes and splenic tissue. Control mice received isotonic saline as the injectate. On day 3, the percentages obtained from PbAc-treated mice showed a decline, reaching their minimum value by day 4. Recovery from erythropoietic suppression appeared to be complete by day 6 or 7; no positive overshoots in 59Fe percentages were found following recovery. These trends were typical for both peripheral red blood cells and spleen. Testosterone was administered to mice receiving saline or PbAc on two consecutive days (days -1 and O). Radioiron uptake percentages for females receiving testosterone and saline showed an abrupt increase on day 4. No accelerative effect due to testosterone was found in recipient males. For females treated with testosterone and PbAc, the radioiron percentages for erythrocytes and spleen paralleled those for females receiving saline only. Male mice treated with both androgen and PbAc demonstrated 59Fe percentages typical of males treated with PbAc alone. 相似文献
12.
Cell proliferation in the prostate complex of the castrate mouse 总被引:1,自引:0,他引:1
Cell proliferation during 100 h of continuous androgen challenge was studied in the seminal vesicle and coagulating gland of Balb/c mice castrated 3 days or 14 days prior to the first daily injection of 250 mug testosterone propionate. Continuous labelling with [3H] thymidine indicated that the seminal vesicle was almost totally responsive to androgen, as early as 3 days after castration, whereas the androgen sensitivity of the coagulating gland increased from 30% at 3 days after castration to 85% at 14 days after castration. In both tissues the magnitude of the proliferative reaction could be related to the extent of cell loss prior to stimulation. The duration of the pre-replicative phase in the response of the seminal vesicle to androgen was 20-25 h both at 3 and 14 days after castration. In the coagulating gland the pre-replicative phase was 40 h at 3 days after castration and 20 h at 14 days after castration. The maximum uptake of [7alpha-3H] testosterone administered to mice 3 days after castration was significantly greater (P less than 0-01) in the seminal vesicle compared to the coagulating gland. At 14 days the seminal vesicle and coagulating gland exhibited a similar capacity for uptake. The in vivo metabolism of [7alpha-3H] testosterone was studied by thin layer chromatography 30 min and 120 min after administration. A high proportion of the radioactivity extracted from all the tissues was associated with highly polar steroids. At 3 days after castration, the seminal vesicle, 2 h after administration of radioactive testosterone, retained a much higher proportion of radioactivity associated with dihydrotestosterone than did the coagulating gland. The localization of steroid in mice 3 days after castration was studied by dry-mount autoradiography at intervals up to 2 h after the injection of [1,2,6,7(n)-3H]-testosterone. A heavier deposition of silver grains was observed over autoradiographs of the seminal vesicle. In the seminal vesicle the grains were primarily located over nuclear areas whereas in the coagulating gland the grains were diffusely distributed over both nuclear areas and over cytoplasmic areas. 相似文献
13.
We previously reported a strain-related difference in basal 3beta-hydroxysteroid dehydrogenase-isomerase (3betaHSD) activity in response to testosterone in cultured Leydig cells. The data suggested that the response to testosterone was androgen receptor mediated and that testosterone was acting via a trans-acting factor distal to the androgen receptor to regulate Leydig cell basal 3betaHSD activity. This study was designed to determine whether the previous reported strain-related difference in basal 3betaHSD activity in response to testosterone was due to a difference at the 3betaHSD protein and/or at the mRNA level. In C57BL/6J Leydig cells, 2.0 microM testosterone significantly decreased basal 3betaHSD immunoreactive mass by day 6 in culture. Treatment with 2.0 microM testosterone and 2.0 microM hydroxyflutamide, an androgen receptor antagonist, negated the inhibitory effect of testosterone on C57BL/6J 3betaHSD immunoreactive mass. Treatment with 2.0 microM testosterone also significantly decreased 3betaHSD mRNA content in C57BL/6J Leydig cells, which was detectable on day 3 in culture. In contrast to Leydig cells from C57BL/6J mice, Leydig cells from C3H/HeJ mice were not susceptible to the inhibitory effect of testosterone on 3betaHSD. Treatment with 2.0 microM testosterone had no detectable effect on C3H/HeJ 3betaHSD immunoreactive mass or mRNA content at any time point in culture. These data indicate that the testosterone-induced loss of basal 3betaHSD activity in C57BL/6J Leydig cells can be accounted for by the loss of 3betaHSD immunoreactive mass, which is preceded by the loss of 3betaHSD mRNA, and that the strain-related difference in the regulation of 3betaHSD is present at all three levels. Thus, the putative trans-acting factor involved in the mechanism whereby testosterone decreases basal 3betaHSD is likely to regulate the amount of 3betaHSD mRNA. 相似文献
14.
The prostate is a highly heterogeneous organ, composed of different types of epithelial and stromal cells organized regionally along the ductal network. Although androgen-stimulated growth and maintenance of the prostate gland primarily involve epithelial cells, it is unclear whether all epithelial cells are androgen dependent. Moreover, the actions of androgens may not be direct; a number of polypeptide growth factors, including transforming growth factor-alpha (TGFalpha), are postulated to mediate androgen action in the rat prostate. In this investigation, using an immunohistochemical technique, we examined the cellular and regional expression of TGFalpha in the rat ventral prostate during postnatal development to adulthood. TGFalpha-immunopositive cells were located throughout the ductal epithelium from postnatal days 5-20. By day 45 and thereafter, regional variation in TGFalpha expression became apparent; epithelial cells in the proximal segment exhibited intense staining, whereas those in the distal segment exhibited negligible staining. These observations were coincident with increased serum testosterone concentrations at puberty. To understand the role of androgen in the expression of TGFalpha in the epithelial cells of the distal and proximal segments of the adult rat ventral prostate, androgen was withdrawn by castration, and testosterone subsequently was administered. Androgen receptor protein expression decreased after castration and reappeared after androgen replacement in both the distal and proximal segments. TGFalpha staining was negligible in epithelial cells of the distal segment of intact adult rats, became prominent by 7 days after castration, but then diminished after the administration of testosterone. Western blot analyses revealed the presence of a specific 30-kDa immunoreactive form of TGFalpha in rat ventral prostate, and its quantity reflected the staining intensities observed in the immunohistochemical studies. These results suggest that TGFalpha expression is negatively regulated by androgen in epithelial cells of the distal segment. In contrast, staining for TGFalpha in epithelial cells of the proximal segment did not change with castration or testosterone administration, suggesting that TGFalpha is not regulated by androgen in this region of the ventral prostate. In summary, TGFalpha expression is differentially regulated among epithelial cells localized in two different regions of the ventral prostate. We hypothesize that TGFalpha may function as a survival factor for epithelial cells which, as a consequence of its expression, become androgen independent and thus escape apoptotic cell death after androgen ablation. 相似文献
15.
DL McCormick KV Rao L Dooley VE Steele RA Lubet GJ Kelloff MC Bosland 《Canadian Metallurgical Quarterly》1998,58(15):3282-3288
The influence of chemical carcinogen, hormonal stimulation, and chronic dietary administration of the synthetic retinoid, N-(4-hydroxyphenyl)-all-trans-retinamide (4-HPR), on the induction of prostate cancer in male Wistar-Unilever rats was determined. Three different tumor induction regimens were used: (a) a single i.v. dose of 50 mg of N-methyl-N-nitrosourea (MNU) per kg body weight, followed by chronic androgen stimulation via s.c. implantation of two silastic capsules containing 40 mg testosterone each; (b) a single i.v. dose of 50 mg of MNU per kg body weight (no testosterone treatment); and (c) chronic androgen stimulation with implanted testosterone capsules (no MNU treatment). In a fourth series of animals, the incidence of spontaneous prostate tumors was determined in groups of rats receiving neither carcinogen nor hormone stimulation. Within each series, parallel groups of animals were fed a control (vehicle-supplemented) diet or control diet supplemented with 4-HPR beginning 1 day after carcinogen administration; retinoid administration was continuous until termination of the study at 450 days. The incidence of accessory sex gland cancer in rats treated sequentially with MNU + testosterone was >60%, in comparison with cancer incidences of <20% in rats receiving MNU only and <5% in rats treated with testosterone only. No spontaneous accessory sex gland tumors were observed in rats receiving no carcinogen and no testosterone. Tumor induction in the accessory sex glands by MNU + testosterone was relatively specific for the prostate: the incidence of carcinoma of the dorsolateral/anterior prostate was more than 5-fold greater than the incidence of cancer present only in the seminal vesicle. 4-HPR conferred no protection against cancer induction in the prostate by any regimen of MNU and/or testosterone. These results demonstrate the importance of both carcinogen exposure and hormone stimulation on the induction of neoplasia in the prostate of Wistar-Unilever rats. 相似文献
16.
Telomeres, the repetitive non-coding DNA sequences found at the ends of all eukaryotic chromosomes, shorten with each cell division. It has been proposed that telomere shortening may be the counting element of a mitotic clock that keeps track of cell divisions; with shortening to a critical length acting as a senescence signal underlying cellular aging. The enzyme telomerase functions to maintain telomere length, thus allowing unlimited cell division, and has been associated with cellular immortalization and cancer. Stem cells have large, perhaps unlimited, replicative capacities. Since these cells are potentially immortal, we reasoned that they might posses active telomerase. We therefore assayed for telomerase activity in the stem cell enriched pools of the androgen-depleted sex accessory tissues in the castrated male rat. Following castration, the ventral prostate and seminal vesicles of the rat involute, losing approximately 90% of their cells by 21 days. These residual glands persist, and are enriched for stem cells, being capable of fully regenerating these glands if testosterone is re-introduced into the animal. We assayed telomerase activity in extracts from normal, involuted, and regenerating ventral prostate and seminal vesicles. Normal glands were found to be telomerase negative, whereas telomerase activity appeared as these glands involuted following castration. Conversely, telomerase activity disappeared during testosterone-induced regeneration of these residual glands. These results provide strong evidence for the ability of androgen to negatively-regulate telomerase activity in stem cell populations of the rat ventral prostate and seminal vesicles. and represent the first in vivo model system for the modulation of telomerase activity. 相似文献
17.
SA McNeill M O'Donnell R Donat A Lessells TB Hargreave 《Canadian Metallurgical Quarterly》1997,177(6):1541-1542
We report on a 68-year-old patient with complete androgen insensitivity syndrome (testicular feminization syndrome) in whom an estrogen-secreting malignant sex cord stromal tumor developed in an intraabdominal testis. We believe this to be the first such case to document estrogen secretion by the tumor. 相似文献
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19.
J Bikowski 《Canadian Metallurgical Quarterly》1999,17(1):197-206
In golden hamsters, seasonal changes in day length act via a pineal-dependent mechanism to regulate feedback and behavioral effects of androgen. Endogenous opiates participate in photoperiodically regulated neuroendocrine functions, but the effects of androgen on expression of the gene encoding POMC, the precursor of beta-endorphin, have been controversial. We used quantitative in situ hybridization to examine regulation of POMC messenger RNA (mRNA) by testosterone and to test the hypothesis that short day lengths act through the pineal gland to amplify POMC mRNA expression. We studied intact hamsters and castrates with or without androgen treatment held in long (14 h of light, 10 h of darkness) or short (5 h of light, 19 h of darkness) days for 10 weeks. POMC gene expression differed with rostral-caudal plane, photoperiod, and surgical treatment (castration and testosterone administration). Testosterone increased the number of silver grains in labeled cells throughout the arcuate nucleus, and short day castrates given androgen consistently had more silver grains per labeled cell than did their long day counterparts. Testosterone exerted an inhibitory effect, however, on the number of POMC mRNA-positive cells, and more POMC mRNA-labeled cells were found in the arcuate nucleus of long than short day castrates treated with testosterone. Photoperiod had no significant influence in castrates not receiving androgen. Testosterone treatment had generally similar effects whether it was begun at the time of castration or 5 weeks later. Pinealectomy blocked the influence of photoperiod on both the mean number of silver grains per labeled cell and the number of labeled cells. The results indicate that day length regulates POMC gene expression when androgen levels are held constant, but that androgen is necessary for photoperiod effects to be expressed. 相似文献
20.
The formation of estrogens from C19 steroids is catalyzed by aromatase cytochrome P450 (P450arom), the product of the cyp19 gene. The actions of estrogen include dimorphic anatomical, functional, and behavioral effects on the development of both males and females, considerations that prompted us to examine the consequences of deficiency of aromatase activity in mice. Mice lacking a functional aromatase enzyme (ArKO) were generated by targeted disruption of the cyp19 gene. Male and female ArKO mice were born with the expected Mendelian frequency from F1 parents and grew to adulthood. Female ArKO mice at 9 weeks of age displayed underdeveloped external genitalia and uteri. Ovaries contained numerous follicles with abundant granulosa cells and evidence of antrum formation that appeared arrested before ovulation. No corpora lutea were present. Additionally the stroma were hyperplastic with structures that appeared to be atretic follicles. Development of the mammary glands approximated that of a prepubertal female. Examination of male ArKO mice of the same age revealed essentially normal internal anatomy but with enlargement of the male accessory sex glands because of increased content of secreted material. The testes appeared normal. Male ArKO mice are capable of breeding and produce litters of approximately average size. Whereas serum estradiol levels were at the limit of detection, testosterone levels were elevated, as were the levels of follicle-stimulating hormone and luteinizing hormone. The phenotype of these animals differs markedly from that of the previously reported ERKO mice, in which the estrogen receptor alpha is deleted by targeted disruption. 相似文献