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Query: UNIPROT:P06889 (Mol)
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Sertoli cell-enriched preparations were obtained by sequential enzyme treatment of testes of 18-20 day old rats, and were maintained in culture in a chemically defined medium. The addition of highly purified follicle-stimulating hormone (FSH) to cells immediately after preparation, or after 48 h in culture, elicited an increase in the level of cyclic adenosine 3',5'-monophosphate (cAMP) when incubated in the presence of 3-isobutyl-1-methylxanthine (MIX). Luteinizing hormone (LH) had no effect on the cAMP levels. The cells cultured in the presence of FSH or dibutyryl cAMP for 48 h incorporated more [3H]leucine into trichloroacetic acid (TCA)-insoluble material than did cells cultured in the basal medium. Cycloheximide abolished the amino acid incorporation into protein precipitated by TCA. The data demonstrate that the Sertoli cell is a target cell for FSH action, and indicate that added dibutyryl cAMP can duplicate the enhancement of amino acid incorporation into protein elicited by FSH.
Mol Cell Endocrinol 1975 Jul
PMID:Effects of follicle-stimulating hormone on cultures of Sertoli cell preparations. 16 4

The incorporation of [2H]thymidine into nuclear DNA was investigated in cultured Sertoli cells prepared from testes of 20-day-old rats. Addition of follicle-stimulating hormone (FSH) or dibutyryl cyclic, 3',5'-adenosine monophosphate (DBCAMP) to the culture medium greatly increased incorporation, expressed either as total amounts of [3H]thymidine incorporated per mug DNA or as the percentage of Sertoli cells with labeled nuclear DNA. No stimulation was observed in cells cultured in the presence of testosterone, insulin or cyclic 3',5'-GMP (cGMP). Light and electron microscopic autoradiographic analysis was employed to establish the identity of Sertoli cells having labeled nuclear DNA. Contaminating spermatogonia, which also took up labeled [3H]thymidine, were excluded from cell counts. In addition, Sertoli cells prepared from testes of irradiated 20-day-old germinal cell depleted rats were also observed to incorporate more [3H]thymidine into nuclear DNA when cultured in a chemically defined medium in the presence of FSH. DNA synthesis was abolished by prior treatment of cells with cytosine arabinoside. In separate experiments, the incorporation of [3H]thymidine into DNA of peritubular myoid cells was shown to be independent of FSH or dbcAMP.
Mol Cell Endocrinol 1976 Feb
PMID:FSH stimulation of DNA synthesis in Sertoli cells in culture. 17 64

The effects of cholera toxin on the responses of cultured Sertoli cells were compared with those elicited by follicle-stimulating hormone (FSH), and N6O2'-dibutyryl-3',5'-cyclic AMP (bu2cAMP). Addition of FSH or cholera toxin increased cAMP levels. Subsequently there was greater rates of conversion of testosterone to 17beta-estradiol, formation of androgen-binding protein (ABP), and incorporation of [3H]thymidine into DNA by Sertoli cells prepared from testes of immature rats and cultured in the presence of either FSH or cholera toxin. Addition of bu2-cAMP also resulted in enhanced rates of formation of ABP, synthesis of 17beta-estradiol and synthesis of DNA. Cholera toxin and bu2-cAMP elicited changes in morphology of cultured Sertoli cells indistinguishable from those following FSH addition. It is concluded that elevated intracellular cAMP levels can duplicate known actions of FSH on cultured Sertoli cells, but the possible obligatory role of cAMP in mediating FSH actions remains to be evaluated.
Mol Cell Endocrinol
PMID:Similarity of responses of cultured Sertoli cells to cholera toxin and FSH. 18 80

Sertoli cells isolated from the testes of 18 to 20-day old rats synthesize estradiol-17 beta when grown in primary culture in the presence of testosterone (5 X 10(-7) M). After an initial lag phase of about 2 hours, follicle-stimulating hormone (FSH) stimulates synthesis of estradiol up to 50-fold, synthesis being approximately linear for 24 hours when medium is changed every 2-6 hours. Luteinizing hormone (LH) causes only a marginal stimulation, at concentrations consistent with contamination with FSH. Dibutyryl cyclic 3',5'-adenosine monophosphate (dbcAMP) (10(-4)M) mimicks the effect of FSH. No significant synthesis occurs in the absence of steroid substrate or in the presence of pregnenolone (5 X 10(-7) M). When cells are pre-incubated for 24 hours with FSH in the absence of testosterone, addition of testosterone results in an immediated increase in estradiol synthesis without a lag phase, suggesting that FSH or dbcAMP are capable of inducing the conditions necessary for stimulation in the absence of testosterone. These observations provide the first direct evidence of estradiol-17 beta synthesis by Sertoli cells from normal animals, and offer evidence that synthesis of this steroid is regulated at the level of the aromatizing enzyme system by FSH and cyclic AMP.
Curr Top Mol Endocrinol 1975
PMID:Synthesis of estradiol-17 beta by Sertoli cells in culture: stimulation by FSH and dibutyryl cyclic AMP. 19 77

Peripheral concentrations of follicle-stimulating hormone (FSH) in male as well as in female animals appear to be partly regulated by inhibin, a protein which is secreted by the gonads. The molecular structure of this substance is still unknown, and the mechanism(s) of its action on the pituitary or hypothalamic level is not clear. Much of the confusion about inhibin stems from the fact that no generally accepted definition of inhibin exists and that fundamentally different biological assay systems have been used by different groups. Therefore this short review starts with a discussion of the definition of inhibin and the assay principles. From the available information on the site of origin of the hormone it appears likely that inhibin is produced in the Sertoli cells of the testis and the granulosa cells of the ovary. The available data on the chemical nature of inhibin suggest that different principles, acting on different sites of the hypothalamic--pituitary axis, might be present in preparations with inhibin-like activity. Finally, with respect to the biological significance of inhibin, it seems that inhibin could play a more important role in the feedback regulation of FSH in the adult female than in the adult male animal.
Mol Cell Endocrinol 1979 Jan
PMID:Inhibin--fact or artifact. 37 71

The formation of androgen-binding protein (ABP) by cultured Sertoli cells, prepared from testes of immature rats, is increased when androgens or follicle-stimulating hormone (FSH) are present in the medium. Testosterone and 5alpha-dihydrotestosterone are equally effective in stimulating the synthesis and secretion of ABP, but non-androgenic steroids examined (progesterone, 17beta-estradiol and corticosterone) are without influence. Maximal increases are observed when androgens are added at the time of cell plating. Cells maintained in culture medium devoid of hormones become progressively less sensitive to subsequent addition of testosterone or FSH. Data are discussed in relation to the sites of androgen requirements for spermatogenesis.
Mol Cell Endocrinol 1977 Mar
PMID:Stimulation by androgens of the production of androgen binding protein by cultured Sertoli cells. 85 27

The penetration of 125I-iodinated rat follicle-stimulating hormone (FSH; labelled by three different techniques) and luteinizing hormone (LH) through the walls of the seminiferous tubules of the rat testis has been studied by injecting the labelled hormone into rats with the efferent ducts of one testis ligated 16 h before the collection of samples of blood and tissues. The concentration of trichloracetic acid-precipitable and immunoprecipitable radioactivity was measured in blood plasma and rete testis fluid and calculated for the total secreted fluid retained in the testis by the ligature, and for the additional tubular fluid from the ligated testis, separated by centrifugation after decapsulating the testis and dispersing the cells. Very little intact hormone penetrated into the testicular fluids, even 16 h after injection of the labelled hormone, and the volume of distribution in the unligated testis of the trichloracetic acid-precipitable radioactivity was only slightly greater than that for markers known to be confined to the extracellular interstitial fluid. This suggests that the labelled hormones do not penetrate readily through the walls of the semiferous tubules into their lumina. Injected inorganic iodiide and trichloracetic acid-soluble 125I-circulating after the injection of iodinated hormones penetrated more rapidly into the tubules, but had not reached equilibrium between the testicular fluids and blood plasma 16 h after injection. Labelled FSH was reasonably stable in the circulation after injection, but 80% of the 125I was not protein-bound 16 h after injection of labelled LH.
Mol Cell Endocrinol 1976 Nov
PMID:The restricted penetration of iodinated rat FSH and LH into the seminiferous tubules of the rat testis. 100 8

Sertoli cells were isolated from testes of 20-day-old rats and were maintained in primary culture. The ability of these cells to synthesise estradiol-17beta from a variety of exogenous substrates, progesterone, testosterone,androstenedione, 19-hydroxyandrostenedione and 19-hydroxytestosterone in the presence and absence of follicle-stimulating hormone (FSH) was examined. In the presence of each of the substrates alone for 24 h the rate of estradiol-17beta synthesis was very low. FSH (NIH-FSH-S11, 5 mug/ml) stimulated estradiol-17beta synthesis 75-fold when added to medium containing testosterone (5 X 10(-7)M) but caused only marginal stimulation when added to medium containing progesterone (5 X 10(-7) M). Both FSH and dibutyryl cyclic AMP (bu2cAMP) stimulated the conversion of each of the substrates, androstenedione, 19-hydroxyandrostenedione and 19-hydroxytestosterone to estradiol-17beta, and the effects were similar to those observed in the presence of testosterone. These data indicate that, under the culture conditions employed, progesterone is not an effective substrate for conversion to estradiol-17beta by Sertoli cells. Estradiol-17beta synthesis was stimulated by FSH in the presence of the C19 steluences the conversion of androgens to estrogens, either directly or indirectly, at the aromatisation step (i.e. the conversion of 19-hydroxylated androgens to estrogens).
Mol Cell Endocrinol 1976 Dec
PMID:Site at which FSH regulates estradiol-17beta biosynthesis in Sertoli cell preparations in culture. 100 11

Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) result from the assembly of a common subunit alpha and a unique subunit beta, expressed in the same cell by single, structurally-related genes. In order to compare the intrinsic stability of the alpha, LH beta and FSH beta mRNA transcripts, we used cultured rat pituitary cells incubated in presence of actinomycin D. Hybridization with 32P-labelled rat cDNA probes showed that the cell content of all three mRNAs decreased with time, but at different rates. Apparent half-lives, estimated as the time necessary to observe a 50% mRNA decay, were 1.0 +/- 0.13 h for FSH beta, 6.5 +/- 0.25 h for alpha and 44 +/- 0.5 h for LH beta, stability thus exhibiting an inverse relation to the sizes of the corresponding mRNAs (approximately 1700, 800 and 700 nucleotides, respectively). Northern analysis revealed that the decline in mRNA abundance was associated with a progressive decrease in the length of mRNAs, most clearly visible for alpha and LH beta. For the most stable LH beta mRNA, shortening was apparent as early as 2 h after exposure to actinomycin D thus preceding neatly the decrease in amount starting at about 10-12 h. In vitro RNase H digestion demonstrated that shortening resulted from a reduction of the length of the poly(A) tract. These data establish that the three mRNAs coding for gonadotropin subunits have different stabilities although they share substantial homology. Diversity in size and sequence essentially resides in untranslated regions in which, we suggest, specific motifs and protein factors may interact to determine mRNA stability.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1992 Oct
PMID:Differential stability of mRNAs coding for alpha and gonadotropin beta subunits in cultured rat pituitary cells. 128 Nov 25

The effects of insulin-like growth factor-binding proteins (IGFBPs) 1 and 3 on steroidogenesis by human granulosa cells has been examined. Both IGFBP-1 and IGFBP-3 produced a dose-related inhibition of IGF-I-stimulated oestradiol accumulation in granulosa cell-conditioned medium with complete reversal of the effects of IGF-I in the presence of a molar excess of binding protein. IGFBPs 1 and 3 also exerted a small (25-40%) but significant and consistent inhibition of oestradiol secretion in response to follicle-stimulating hormone (FSH) alone. The progesterone response to IGF-I was inhibited by IGFBPs 1 and 3 but there was no effect on FSH-stimulated progesterone production. These data support the concept of a physiologically important intraovarian IGF system in the human ovary and demonstrate an unequivocally inhibitory effect of IGFBPs 1 and 3 on IGF-I-stimulated granulosa cell steroidogenesis.
Mol Cell Endocrinol 1992 Nov
PMID:Inhibitory effects of insulin-like growth factor-binding proteins on steroidogenesis by human granulosa cells in culture. 128 89


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