ISSN:0098-4108    

DOI:10.1080/15287397809529657

出版商:Taylor & Francis Group    

年代:1978

数据来源: Taylor

摘要:

Analysis of X‐ray data concerning 277 estranes, androstanes, and pregnanes and comparison with progesterone receptor binding data have prompted the following observations.

ISSN:0098-4108    

DOI:10.1080/15287397809529658

出版商:Taylor & Francis Group    

年代:1978

数据来源: Taylor

摘要:

Association and dissociation rate constants of steroid complexes with progesterone‐binding globulin (PBG) and with corticosteroid‐binding globulin have been determined, utilizing the fluorescence quenching phenomenon observed on steroid binding to protein. Stopped‐flow techniques were used in most cases. The dissociation rates of the complexes with steroid‐binding proteins of serum are much greater than those of steroid‐receptor complexes, in accordance with the biological functions of these two types of proteins. Association of steroids with PBG is accompanied by conformational changes in both components of the complexes. Chemical modification of tryptophan, lysine, and tyrosine in PBG results in inactivation of the binding site; complex formation with progesterone protects against this inactivation. A comparison of the affinity constants of PBG complexes with steroids of different structures leads to a conceptual image of the binding site and to localization of the various forces of interaction over the binding site area.

ISSN:0098-4108    

DOI:10.1080/15287397809529659

出版商:Taylor & Francis Group    

年代:1978

数据来源: Taylor

摘要:

The relevance of metabolism of steroids in target tissues to hormonal action is discussed. Two mechanisms of metabolic regulation at the cellular level are considered: formation of active steroids from steroidal prehormones, and controlled conversion of the active compound to inactive metabolites. Factors regulating the direction in which interconversions between active hormones and inactive metabolites preferentially proceed are mentioned; methods of estimating the preferred directionin vitroandin vivoare described and examples are given. The estradiol‐estrone system in human endometrium is used to describe a case in which a hormone (progesterone) induces an enzymatic activity (17 β‐hydroxysteroid dehydrogenase) and lowers the intracellular/extracellular ratio of concentrations of the active hormone (estradioi) by increasing its conversion to an inactive, or less active, metabolite (estrone). That hormone metabolism can effectively determine the level of unbound hormone available for association to receptors is shown with published data on estradioi in human endometrium, using a kinetic analysis in which binding and Michaelis‐Menten equations are combined.

ISSN:0098-4108    

DOI:10.1080/15287397809529660

出版商:Taylor & Francis Group    

年代:1978

数据来源: Taylor

摘要:

In pursuit of a model system in which to determine whether exposure to progesterone is necessary for mammary epithelial cells to develop their differentlative potential, hormone‐dependent growth of the mammary epithelial rudiment in adult male mice has been reexplored. The formation of ductal cells can be effected by administration of estradiol in the absence of endogenous progesterone and glucocorticoid, using odrenalectomized‐castrated animals. The resulting epithelium contains three times more lactose synthetase activity, per epithelial cell, than that in midpregnant mice. The blood spermidine level in these doubly operated animals was similar to the concentration of spermidine required to substitute effectively for glucocorticoid during mammary differentiationin vitro. It is suggested that spermidine can partially supplant glucocorticoidin vivoin milk protein synthesis. It is also concluded that, unlike other secondary sex tissues, mammary cells do not require exposure to progesterone during their ontogeny in order to realize their differentiative potential. The positive role of this steroid in mammary development is apparently limited to its effect on the formation of alveolar structures.

ISSN:0098-4108    

DOI:10.1080/15287397809529661

出版商:Taylor & Francis Group    

年代:1978

数据来源: Taylor

摘要:

There has been an increasing interest in the sulfate conjugates of estrogens as important metabolites in steroid hormone homeostasis and activity. In women estrogen sulfates have been known as major components of plasma originating from ovarian secretion and hepatic metabolism. However, only recently has the capacity to sulfurylate estrogens been demonstrated in estrogen target tissues. Porcine uterus estrogen sulfotransferase appears only after the first complete estrous cycle. Following puberty, gilt uterine sulfurylation of estrogens is extremely active during diestrus, whereas estrogen sulfotransferase is not present during estrus. This cycling of estrogen sulfurylation in porcine and human uteri can be related directly to plasma progesterone levels.

ISSN:0098-4108    

DOI:10.1080/15287397809529662

出版商:Taylor & Francis Group    

年代:1978

数据来源: Taylor

摘要:

Forage plant estrogens occur at high levels in certain forage species. Such levels are responsible for reproductive and other effects in animals. Current progress regarding the chemical, metabolic, and biological effects, as well as occurrence of the several naturally occurring forage estrogens, is described. Forage estrogens occur as natural plant responses to foliar and other plant diseases. Their potency in animals is approximately 1/1000 to 1/10,000 that of the principal animal hormones such as estradiol. Coumestans and isoflavones comprise the two principal classes of forage estrogens, with coumestrol and genistein being the most potent and predominant of each class. Only very low levels of the coumestans occurred in alfalfa leaf protein concentrates prepared at alkaline pH.

ISSN:0098-4108    

DOI:10.1080/15287397809529663

出版商:Taylor & Francis Group    

年代:1978

数据来源: Taylor

摘要:

Some DDT analogs are estrogenic, particularly o,p'‐DDT, which comprises approximately 15–20% of the commercial DDT mixture. Whether this compound or its metabolites are active has not been established. In fact, the data obtained thus far are more confusing than enlightening. For example, CC/4pretreatment of immature female rats has been reported to inhibit or enhance estrogenic activity of o,p'‐DDT, and SKF‐525A pretreatment has been reported to enhance or not alter the estrogenic effect. Although o,p'‐DDT inhibits binding of estradiol to the estrogen receptor from rat or human at low levels (∼7–10 μM)in vitro, higher levels are required to inhibit nuclear binding of [3H] estradiol in incubated whole uteri. Furthermore, o,p'‐DDT appears to be neither estrogenic nor antiestrogenic in anin vitroestrogen assay. Methoxychlor appears to be “activated” by metabolism, and it is probable that phenolic metabolites are responsible for its estrogenic activity. Since chlorinated hydrocarbons often enhance the metabolism of steroids and may reduce circulating levels of steroids, interactions of the exogenous hormonaliy active agents with steroid receptors may be self‐potentiatingin vivo.

ISSN:0098-4108    

DOI:10.1080/15287397809529664

出版商:Taylor & Francis Group    

年代:1978

数据来源: Taylor

摘要:

The oxidative metabolism of some exogenous compounds, and possibly some endogenous compounds as well, can lead to the formation of reactive metabolites. These intermediates react as electrophiles, and they lead in some instances to cell death or cell transformation. Three routes (other routes are also known) of toxicity are discussed. These are the epoxide/dihydrodiol pathway, the catechol/o‐quinone pathway, and the alkylation pathway. The possible formation of electrophiles from diethylstilbestrol, from natural estrogens, and from ethynylestradiol is discussed in terms of protein binding. Protein binding is presumptive evidence of electrophile formation, but it does not necessarily indicate that the parent compound is highly cytotoxic, mutagenic, or carcinogenic. Mutagenic and carcinogenic activity is presumed to require reaction of an electrophile with nuclear material. There is evidence for protein binding for these estrogens (diethylstilbestrol, natural estrogens, ethynylestradiol) as a consequence of oxidative metabolism.

ISSN:0098-4108    

DOI:10.1080/15287397809529665

出版商:Taylor & Francis Group    

年代:1978

数据来源: Taylor

摘要:

The uterotropic and ontiuterotropic effects of a variety of structural derivatives of the nonsteroidal antiestrogen tamoxifen have been determined in the rat and the mouse. One derivative, monohydroxytamoxifen, was found to be a potent antiestrogen in the rat, with a high affinity for the estrogen receptor.

ISSN:0098-4108    

DOI:10.1080/15287397809529666

出版商:Taylor & Francis Group    

年代:1978

数据来源: Taylor