Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 83
Filtrar
1.
Science ; 271(5253): 1291-3, 1996 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-8638113

RESUMO

Heterosexual transmission by vaginal intercourse accounts for most transmission of human immunodeficiency virus-type 1 (HIV-1) in Africa and Asia but is less important in the HIV-1 epidemics of the United States and Western Europe. Epithelial Langerhans' cells (LCs) represent a possible source of initial cell contact for vaginal infection. Fifteen primary isolates of HIV-1 from U.S. homosexuals and 18 HIV-1 isolates from Thailand heterosexuals were evaluated for growth in LCs of U.S. origin. All the viruses from the Thai heterosexuals, which were subtype E, grew more efficiently in the LCs than any of the viruses from the U.S. homosexuals, which are subtype B. These results suggest that LC tropism is associated with the efficiency of heterosexual transmission of HIV.


Assuntos
Infecções por HIV/transmissão , HIV-1/crescimento & desenvolvimento , Células de Langerhans/virologia , Comportamento Sexual , Doenças Virais Sexualmente Transmissíveis/transmissão , Linhagem Celular , Células Cultivadas , Proteína do Núcleo p24 do HIV/análise , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/isolamento & purificação , Homossexualidade Masculina , Humanos , Macrófagos/virologia , Masculino , Monócitos/virologia , Doenças Virais Sexualmente Transmissíveis/virologia , Linfócitos T/virologia , Tailândia , Estados Unidos , Replicação Viral
2.
Endocrinology ; 101(5): 1552-8, 1977 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-199421

RESUMO

Immunoassayable (I) and bioassayable (B) ACTH activity is present in extracts of extensively washed human placental tissue and dispersed viable trophoblasts (Tr). Similar concentrations (I) (1.7-2.7 ng/g) are present in term placentas from elective cesarian section or vaginal delivery and from plancentas obtained by prostaglandin-induced abortion at 12, 15 and 18 weeks of gestation. Oral dexamethasone (8-12 mg) administered over an 8-48 h period prior to delivery does not significantly alter placental ACTH content. B-ACTH concentrations are 31-40% of I-ACTH. Sephadex G-50 filtration of term placental homogenates demonstrates two I-ACTH peaks, one eluting in the void volume and the other eluting in the region of synthetic hACTH1-39. When Tr are incubated in tissue culture medium, ACTH content of cells and of medium is significantly greater than pre-incubation levels.


Assuntos
Hormônio Adrenocorticotrópico/biossíntese , Placenta/metabolismo , Dexametasona/farmacologia , Feminino , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Trofoblastos/efeitos dos fármacos , Trofoblastos/metabolismo , Tripsina/farmacologia
3.
J Clin Endocrinol Metab ; 77(5): 1367-71, 1993 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8077334

RESUMO

Basic fibroblast growth factor (bFGF) is an angiogenic and mitogenic peptide that may have modulatory effects in the adult ovary and uterus. The FGF receptor is a tyrosine kinase and has similar affinity for both acidic FGF and bFGF. The ligand-binding portion of the receptor has three immunoglobulin-like domains. bFGF and the FGF receptor have been localized in the fetal rat ovary and Mullerian duct. bFGF is a proliferative agent recently shown to be vital for long term cultures of mouse fetal primordial germ cells. Expression of bFGF and FGF receptor mRNA have not heretofore been reported in human fetal ovary and uterus. We prepared RNA from whole human fetal ovaries and uteri at 10, 15, 19, and 22 weeks gestation. After reverse transcription of the RNA into cDNA, we used polymerase chain reaction (PCR) primers directed to specific portions of bFGF and the FGF receptor and performed PCR amplification using the fetal cDNA. We found mRNA expression of bFGF and two forms of FGF receptor in all fetal ovaries and uteri at these developmental stages. One of the PCR products for the FGF receptor was the sequence that contained three immunoglobulin-like domains, whereas a second PCR-amplified fragment was consistent with a FGF receptor mRNA that has a 267-basepair deletion in the first immunoglobulin-like loop. We conclude that bFGF and two forms of the FGF receptor mRNA are expressed in human fetal ovary and uterus. The finding that both bFGF and the FGF receptor are concurrently expressed suggests that bFGF may serve as an autocrine or paracrine modulator during early development of the human reproductive tract.


Assuntos
Feto/metabolismo , Fator 2 de Crescimento de Fibroblastos/genética , Ovário/embriologia , RNA Mensageiro/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Útero/embriologia , Sequência de Bases , Desenvolvimento Embrionário e Fetal , Feminino , Humanos , Sondas Moleculares/genética , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Receptores de Fatores de Crescimento de Fibroblastos/genética
4.
J Clin Endocrinol Metab ; 69(6): 1221-4, 1989 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2584357

RESUMO

The effects of nicotine and cotinine on fetal adrenal 11 beta- and 21-hydroxylase were examined using enzymatic and spectral techniques. The addition of nicotine or cotinine to preparations of adrenal mitochondria yielded a type II cytochrome P-450 binding spectrum. The apparent spectral dissociation constants (Ks) for nicotine and cotinine binding to mitochondrial cytochrome P-450 were 20 and 19 microM, respectively. The addition of nicotine to preparations of adrenal microsomes yielded a type II cytochrome P-450 binding spectrum, with an apparent Ks of 70 microM. Adrenal mitochondrial 11 beta-hydroxylase was assayed by measuring the conversion of deoxycorticosterone to corticosterone. Nicotine and cotinine competitively inhibited 11 beta-hydroxylase, with apparent Michaelis-Menten inhibition constants (Ki) of 9.9 and 9.0 microM, respectively. Nicotine competitively inhibited microsomal 21-hydroxylase, with an apparent Ki of 110 microM. Cotinine, in concentrations as high as 1 mM, did not inhibit 21-hydroxylase. These results suggest that nicotine and cotinine inhibit 11 beta-hydroxylase by binding to the heme iron of the cytochrome P-450 component of this enzyme system. Inhibition of 11 beta-hydroxylase could contribute to the altered pattern of steroidogenesis observed in smokers.


Assuntos
Glândulas Suprarrenais/embriologia , Cotinina/farmacologia , Nicotina/farmacologia , Pirrolidinonas/farmacologia , Esteroide 11-beta-Hidroxilase/antagonistas & inibidores , Esteroide Hidroxilases/antagonistas & inibidores , Glândulas Suprarrenais/enzimologia , Feminino , Feto , Humanos , Cinética , Gravidez
5.
J Clin Endocrinol Metab ; 81(8): 3073-6, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8768877

RESUMO

Peptide growth factors are thought to be involved in adult ovarian regulatory functions. However, little is known about the role of growth factors in human fetal ovarian development. This study is an attempt to identify and localize transforming growth factor-alpha (TGF alpha), epidermal growth factor (EGF), and EGF receptor (EGF-R) in human fetal ovaries. Ovaries were obtained from first and second trimester elective abortuses. Immunohistochemistry was performed on paraffin sections of these specimens after fixation. We examined the sections microscopically using the specific antibodies against TGF alpha, EGF, and EGF-R. Phosphate-buffered saline and preimmune IgG were used as negative controls. First and second trimester ovaries stained positively for all three proteins. Staining was significantly more intense in the oocytes than in the stroma. Negative controls did not stain. These results combined with our previous demonstration of messenger ribonucleic acid for these growth factors suggest roles for TGF alpha, EGF, and EGF-R in human fetal ovarian development. The strong staining in the oocytes suggests a possible autocrine or paracrine role of these growth factors in human oocyte growth in utero.


Assuntos
Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/metabolismo , Feto/metabolismo , Ovário/embriologia , Fator de Crescimento Transformador alfa/metabolismo , Feminino , Idade Gestacional , Humanos , Imuno-Histoquímica , Ovário/metabolismo , Distribuição Tecidual
6.
J Clin Endocrinol Metab ; 47(6): 1236-9, 1978 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-263347

RESUMO

The concentrations of T4, T3, rT3, and TSH were measured at term pregnancy in maternal and umbilical plasma and in amniotic fluid of 11 normal patients who received 8-16 mg dexamethasone 3-48 h before elective cesarean section and of 10 control patients who received no dexamethasone. The mean (+/- SE) concentrations of T4 (micrograms per dl) in maternal and umbilical plasma of dexamethasone-treated patients (12.5 +/- 0.9 and 13.0 +/- 0.9) were not significantly different (P less than 0.05) from those of the control patients (13.9 +/- 1.5 and 10.4 +/- 0.6, respectively). The mean (+/- SE) maternal plasma concentrations of T3 and rT3 (nanograms per dl) of dexamethasone-treated patients (204 +/- 6 and 82 +/- 11) were not significantly different (P less than 0.05) from those of the control patients (201 +/- 26 and 72 +/- 6, respectively). However, the mean (+/- SE) concentrations of T3 and rT3 (nanograms per dl) in umbilical plasma of dexamethasone-treated patients (106 +/- 13 and 360 +/- 35) were 3- and 2-fold and significantly higher (P less than 0.05) than those of the control group (39 +/- 6 and 195 +/- 19, respectively). No significant differences (P less than 0.05) were observed between the mean concentrations of TSH (microunits per ml) in maternal and umbilical plasma of dexamethasone-treated patients (2.5 +/- 0.5 and 3.0 +/- 1.0) and those of the control group (2.8 +/- 0.5 and 6.9 +/- 2.7, respectively). Under the conditions studied, no differences in the mean concentrations of amniotic fluid T4, T3, rT3, or TSH were observed between the two groups of patients (P less than 0.05). The increase of T3 and rT3 levels in umbilical plasma after dexamethasone administration indicates alteration in fetal thyroid economy.


Assuntos
Dexametasona/farmacologia , Sangue Fetal/metabolismo , Troca Materno-Fetal , Glândula Tireoide/efeitos dos fármacos , Hormônios Tireóideos/sangue , Feminino , Humanos , Gravidez , Glândula Tireoide/embriologia , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Tri-Iodotironina Reversa/sangue
7.
J Clin Endocrinol Metab ; 42(1): 98-104, 1976 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1249198

RESUMO

Serum concentrations of total and free thyroxine (T4 and FT4) and total and free triiodothyronine (T3 and FT3) were measured in normal pregnant women, in patients with toxemia of pregnancy, and in patients with gestational trophoblastic disease (GTD). In normal pregnancy, FT4 and FT3 levels remained normal while T4 and T3 levels were elevated. In patients with pre-eclampsia, the mean serum T3 concentration was significantly lower than that of normal pregnancy and the serum FT3 concentrations in three out of nine patients were below the normal pregnancy range. The mean serum T4 and FT4 concentrations in patients with pre-eclampsia were, however, significantly higher than those in normal pregnant women. In patients with GTD without signs of hyperthyroidism, the mean serum total and free T4 concentrations were 43 and 92% higher than those in normal pregnancy (P less than 0.02), and many patients had levels above the range of values observed in normal pregnant women. The mean serum total and free T3 concentrations in GTD patients without signs of hyperthyroidism were not different from those of normal pregnancy (P less than 0.05). In the single GTD patient with hyperthyroid crisis, the s. erum FT4 concentration was within the range seen in GTD patients without signs of hyperthyroidism. Her serum FT3 concentration was, however, much higher than the ranges in normal pregnancy or in GTD patients without clinical hyperthyroidism. Higher than normal FT4 levels were found in patients with and without elevated hCG levels.


Assuntos
Complicações na Gravidez/sangue , Gravidez , Tiroxina/sangue , Tri-Iodotironina/sangue , Feminino , Humanos , Pré-Eclâmpsia/sangue , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez
8.
J Clin Endocrinol Metab ; 43(1): 80-5, 1976 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-947945

RESUMO

Plasma cortisol (F), cortisone (E), and progesterone (P), were measured in the umbilical vein (UV), umiblical artery (UA), and maternal peripheral vein (MPV) of 17 normal patients, and of 8 patients carying anencephalic fetuses. The plasma F in MPV of patients undergoing vaginal delivery after labor of spontaneous onset was significantly higher than that of patients delivered by elective cesarean section, whereas the plasma F concentrations in the UA or UV of the 2 groups were not statistically different from each other. The anencephalic fetuses had UA plasma F and E concentrations which were significantly lower than those of normal fetuses, suggesting that a main portion of UA cortisol and cortisone originates in the fetal adrenal. The UV and MPV plasma F and E concentrations of patients carrying anencephalic fetuses did not differ, however, from those of normal patients, suggesting that these UV corticoids are derived mainly from maternal sources. The amniotic fluid cortisol levels of the patients carying anencephalic fetuses were lower than those observed in the normal pregnancies, suggesting that amniotic fluid cortisol is derived mainly from fetal sources.


Assuntos
Anencefalia/sangue , Cortisona/sangue , Sangue Fetal , Hidrocortisona/sangue , Feminino , Humanos , Gravidez , Progesterona/sangue , Artérias Umbilicais , Veias Umbilicais
9.
J Clin Endocrinol Metab ; 46(3): 365-8, 1978 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-752028

RESUMO

The concentrations of reverse triiodothyronine (3,3',5'-T3 or rT3) in amniotic fluid (AF) were measured by radioimmunoassay in 81 patients with various complications of pregnancy and in 39 normal pregnant patients at equivalent gestational age. In normal pregnancy, AFrT3 concentrations decreased with advancing gestational age. At 21-25, 26-30, 31-35, and 36-40 weeks of normal pregnancy, AFrT3 concentrations (mean +/- SE) were 353 +/- 62 (n = 6), 131 +/- 49 (n = 7), 94 +/- 25 (n = 14), and 93 +/- 5 (n = 20) ng/dl, respectively (ranges: 200-600, 57-350, 66-135, and 50-135). Both normal and supranormal values of AFrT3 were found in patients with complicated pregnancy. In patients with RH isoimmune disease, higher than normal AFrT3 concentrations were associated with seriously affected or gravely ill fetuses wheras normal AFrT3 concentrations predicted a more favorable outcome. There was a good correlation between AFrT3 and AF pigment (deltaOD450) levels (r = 0.70, P less than 0.001). In complicated pregnancy other than erythroblastosis fetalis, AFrT3 concentrations were not of any prognostic significance, and there was no correlation between AFrT3 and lecithin/spingomyelin ratio. The data suggest that AFrT3 determination may help in the assessment of the fetal condition in erythroblastosis fetalis.


Assuntos
Líquido Amniótico/análise , Complicações na Gravidez/metabolismo , Tri-Iodotironina Reversa/análise , Tri-Iodotironina/análise , Feminino , Humanos , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Radioimunoensaio
10.
J Clin Endocrinol Metab ; 79(1): 126-33, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7517945

RESUMO

Peptide growth factors are postulated to have a role in uterine maturation during organogenesis. The purpose of this investigation was to establish a model to study human fetal uterine development. To that end, we describe an in vitro culture system and have characterized the cell types present during the period of uterine maturation. In addition, we evaluated the pattern of growth factor receptor gene expression in these cultured cells. Uteri were dissected from human first and second trimester fetuses (n = 20). Characterization studies were performed against three intermediate filament proteins, cytokeratin, vimentin, and desmin, and against a fibroblast-associated cell surface antigen. Ribonucleic acid was extracted from pure stroma-like cultures, and reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify sequences specific for the epidermal growth factor receptor (EGF-R), fibroblast growth factor receptor (FGF-R), and the insulin receptor (I-R). Two predominant cell types were identified in the cultured fetal tissue: stroma-like cells and clusters of uterine epithelium. Immunofluorescent studies demonstrated positive expression of cytokeratin, vimentin, and a fibroblast-associated antigen in the fetal stroma-like cells, in contrast to adult stromal cells, which consistently expressed only vimentin. Using RT-PCR, the uterine cells were positive for the EGF-R, two forms of the FGF-R, and two forms of the I-R. In conclusion, we provide the first report of a human fetal cell culture system. Characterization studies of fetal stroma-like cells demonstrate immunoreactivity to vimentin, cytokeratin, and a fibroblast antigen, in contrast to the adult stromal cell, which consistently expressed only vimentin. Using RT-PCR, we found that messenger ribonucleic acids for the EGF-R and two forms of both the FGF-R and I-R are expressed. This model may be useful for studying the dynamics of human uterine development in vitro.


Assuntos
Receptores ErbB/genética , Expressão Gênica , Receptores de Fatores de Crescimento de Fibroblastos/genética , Útero/embriologia , Antígenos de Superfície/análise , Sequência de Bases , Células Cultivadas , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Desmina/análise , Feminino , Fibroblastos/imunologia , Imunofluorescência , Idade Gestacional , Humanos , Queratinas/análise , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismo , Útero/química , Útero/metabolismo , Vimentina/análise
11.
J Clin Endocrinol Metab ; 43(1): 208-14, 1976 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-133115

RESUMO

A pregnancy with placental sulfatase deficiency was suspected when a 36-year-old patient at 41 weeks of gestation was found to have extremely low urinary estriol excretion and an otherwise normal prenatal course. The maternal plasma levels of estriol and estradiol 17-beta (E2) were extremely low and estetrol (E4) was undetectable (less than 40 pg/ml), whereas dehydroepiandrosterone sulfate (DS) was normal. THE AMNIOTIC Fluid DS concentration was 22-fold higher than the mean of normal pregnancy, while that of dehydroepiandrosterone (D) and androstenedione (A) was normal. Following intravenous infusion of 50 mg DS, no rise of plasma E2 was noted and plasma E4 levels remained undetectable. At 42 weeks of pregnancy, after induction of labor failed, a healthy male infant was delivered by cesarean section. The umbilical vein (UV) and umbilical artery (UA) levels of DS were extremely high, and those of E2 and E4 were subnormal. The UA level of A was normal and the levels of D and testosterone were slightly elevated. In vitro studies of placental microsomes and the 10,000 x g supernantant confirmed the diagnosis of placental sulfatase deficiency. The infant at 6 months of age had normal growth and development and normal peripheral plasma DS concentration.


Assuntos
Doenças Placentárias/diagnóstico , Placenta/enzimologia , Sulfatases/deficiência , Adulto , Desidroepiandrosterona/metabolismo , Estriol/urina , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Gravidez
12.
J Clin Endocrinol Metab ; 49(5): 687-99, 1979 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-489711

RESUMO

The concentrations of steroids in antral fluid, the number of granulosa cells, the status of the oocyte, and the diameter of each follicle were determined in human ovaries so that follicles at each stage of the menstrual cycle could be classified as large (greater than or equal to 8 mm diameter) or small (less than 8 mm diameter) and healthy or atretic. The granulosa cells and thecal-enriched tissue from each follicle and the stromal tissue from each ovary were cultured for 6 days in vitro. The amounts of progesterone (P), androstenedione (delta 4), testosterone, dihydrotestosterone, estrone, and estradiol (E2) generated by the different tissues were measured on days 0, 2, 4, and 6 of culture. It was found that granulosa cells, thecal tissue, and stromal tissue all have the biosynthetic capacity to produce P, delta 4, testosterone, dihydrotestosterone, estrone, and E2. No individual steroid-secreting compartment of the ovaries studied, whether part of the follicle or of the stroma, had the exclusive capability of producing any of the above-named steroids at any stage of the menstrual cycle or at any stage of antral follicle growth or atresia. Although the steroids produced by the human follicle appear not to be unique to any one cell type, the patterns of steroidogenesis by the granulosa and thecal compartments differ from one another and from the stroma throughout follicular maturation and atresia. During follicular development, granulosa cells produce large amounts of E2 and small amounts of delta 4. During the preovulatory phase, cells from large follicles (greater than or equal to 8 mm diameter) differentiate from an estrogen-secreting state into a P- and, to a lesser extent, an delta 4-secreting one. By contrast, during follicular atresia, granulosa cells continue to synthesize delta 4, but their capacity to synthesize estrogen is substantially reduced. Furthermore, granulosa cells from atretic follicles are incapable of transforming from an androgen-secreting state into a P-secreting one in tissue culture. During follicular growth, thecal tissue secretes about 2--3 times more delta 4 than E2. By contrast, during follicular atresia, thecal tissue retains its capacity to synthesize delta 4 but loses much of its capacity to synthesize E2. The in vitro capacity of thecal tissue to produce steroids exceeds that of the stroma (on a per weight basis) from 2- to 500-fold. Thecal tissue from healthy but not from atretic follicles is capable of differentiating from an androgen- and estrogen-secreting state to a predominantly P-secreting one in tissue culture. It is postulated that although steroid synthesis may not be rigidly compartmentalized during follicular development, appreciable amounts of the steroids secreted by the granulosa and theca may enter different compartments before leaving the ovary...


Assuntos
Androgênios/biossíntese , Estrogênios/biossíntese , Células da Granulosa/metabolismo , Ovário/metabolismo , Progesterona/biossíntese , Adulto , Androstenodiona/biossíntese , Células Cultivadas , Di-Hidrotestosterona/biossíntese , Estradiol/biossíntese , Estrona/biossíntese , Feminino , Humanos , Menstruação , Pessoa de Meia-Idade , Folículo Ovariano/metabolismo , Testosterona/biossíntese
13.
J Clin Endocrinol Metab ; 61(6): 1220-2, 1985 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2997263

RESUMO

We undertook a study designed to evaluate whether it is feasible to suppress fetal adrenal secretion of androgens at mid-pregnancy by giving dexamethasone (DX) to the mother. Levels of DX and adrenal steroids were measured in maternal and cord plasma of 13 DX-treated and 16 untreated mothers undergoing abortion at 18-20 weeks of pregnancy. Maternal adrenal suppression was evidenced by a sharp fall of plasma cortisol (F), cortisone (E), corticosterone (B), and dehydroepiandrosterone sulfate (DHEA-S). However, in cord blood no fall of DHEA-S or corticosterone sulfate (BS) was found up to 20 hours after DX administration, and cord plasma ACTH remained detectable. The failure of DX to suppress the fetal adrenal at mid-pregnancy suggests that this drug would not be effective in the intrauterine treatment of congenital adrenal hyperplasia (C.A.H.).


Assuntos
Corticosteroides/sangue , Dexametasona/farmacologia , Sangue Fetal/análise , Hormônio Adrenocorticotrópico/sangue , Corticosterona/sangue , Cortisona/sangue , Desidroepiandrosterona/análogos & derivados , Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona , Dexametasona/sangue , Feminino , Idade Gestacional , Humanos , Hidrocortisona/sangue , Troca Materno-Fetal , Gravidez
14.
J Clin Endocrinol Metab ; 50(4): 755-63, 1980 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7364931

RESUMO

The status of oocytes, the follicular fluid concentrations of steroids, and the in vitro steroidogenic capacities of stromal tissue, thecal tissue, and granulosa cells from a 15-yr-old girl with primary amenorrhea, ovarian hyperandrogenism, insulin-resistant diabetes mellitus, and acanthosis nigricans were compared to those from normal adult human ovaries. Most oocytes (95%) in the antral follicles recovered from the hyperandrogenic ovaries were degenerative, and the antral fluid levels of testosterone were 30- to 200-fold higher than those in normal ovaries. Granulosa cells from the hyperandrogenic ovaries produced mainly estradiol as did those from normal healthy follicles. The thecal tissues produced 2- to 6-fold more androgen than similar tissues from normal ovaries. However, the stroma from the hyperandrogenic ovaries produced 49- to 250-fold more testosterone than that generated by normal tissues. These data suggest that the removal of stromal tissue as well as follicular tissue from patients with certain types of hyperandrogenism may sometimes contribute to a reduction in androgen secretion.


Assuntos
Amenorreia/metabolismo , Androgênios/metabolismo , Estrogênios/metabolismo , Hirsutismo/metabolismo , Ovário/metabolismo , Virilismo/metabolismo , Adolescente , Adulto , Androgênios/sangue , Células Cultivadas , Estrogênios/sangue , Feminino , Células da Granulosa/metabolismo , Humanos , Pessoa de Meia-Idade , Folículo Ovariano/metabolismo , Valores de Referência
15.
Mol Cell Endocrinol ; 80(1-3): 75-82, 1991 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-1955083

RESUMO

Insulin-like growth factor-II (IGF-II) is postulated to have autocrine and/or paracrine functions in developing fetal tissues, but has never been reported in human fetal reproductive organs. The forms of IGF-II found in normal human serum include a 67 amino acid form and a variant form resulting from alternate splicing of the mRNA such that Ser-29 is replaced by four other amino acid residues. We studied the expression of mRNA encoding IGF-II in human fetal ovaries and uteruses of 10, 15, 19 and 22 weeks of gestation. By reverse transcription followed by polymerase chain reaction (PCR), we identified the co-expression of two mRNAs encoding IGF-II in all developmental stages of fetal ovaries and uteruses tested. One of the PCR amplified fragments was 9 nucleotides larger than the other. The PCR amplified ovarian and uterine DNA fragments were mapped by digestion with the restriction endonucleases AvaII and PvuII and both the IGF-II fragment and the larger IGF-II fragment produced the anticipated DNA patterns by gel electrophoresis. The PCR amplified DNA fragments were cloned and sequenced to confirm that the expressed mRNAs encoded IGF-II and variant IGF-II. We conclude that IGF-II and variant IGF-II mRNA co-expression occurs in the human fetal female genital tract and that the two forms of the growth factors may have physiologic roles in reproductive tract development.


Assuntos
Fator de Crescimento Insulin-Like II/genética , Ovário/metabolismo , Útero/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , DNA , Feminino , Variação Genética , Humanos , Dados de Sequência Molecular , Ovário/embriologia , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismo , Útero/embriologia
16.
Mol Cell Endocrinol ; 39(1): 31-7, 1985 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-2982677

RESUMO

hCG is a known stimulator of mouse thyroid in vivo. Studies were therefore performed to ascertain whether the thyroid-stimulating activity of hCG in the mouse could also be demonstrated by the in vitro techniques that had failed to show any activity of hCG in the human thyroid. When labeled with 125I and incubated at 22 degrees C in 20 mM Tris-0.5% bovine serum albumin (Tris-BSA), pH 7.45, with increasing concentrations (70-300 micrograms protein/ml) of a mouse thyroid fraction, a purified hCG preparation [( 125I]hCG) showed 5-12% specific binding. In contrast, its binding to a human thyroid particulate fraction, over the same range of protein concentrations, did not exceed 1%. When similar studies were performed at 37 degrees C in 10 mM Tris-50 mM NaCl-0.5% BSA, pH 7.45, [125I]hCG showed no detectable binding either to the human or the mouse thyroid fractions. At concentrations ranging from 1 to 20 mIU/ml (0.9-18 X 10(-9) M), bTSH stimulated cAMP release from human thyroid slices into the medium in a dose-dependent manner. In contrast, hCG concentrations from 10(3) to 10(4) IU/ml (2-20 X 10(-6) M) were without effect on cAMP release. bTSH, at concentrations of 4.5 and 9.0 mIU/ml (4 and 8 X 10(-9)M), stimulated cAMP release from the mouse thyroid, producing in the medium approximately 11- and 28-fold increases in cAMP concentration. hCG also stimulated cAMP release from the mouse thyroid, the increases being approximately 2.3- and 1.8-fold, in the presence of 2270 and 4540 IU/ml (4.5 and 9.0 X 10(-6) M), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Gonadotropina Coriônica/farmacologia , Glândula Tireoide/efeitos dos fármacos , Animais , Gonadotropina Coriônica/metabolismo , AMP Cíclico/biossíntese , Humanos , Técnicas In Vitro , Radioisótopos do Iodo , Masculino , Camundongos , Especificidade da Espécie , Testículo/metabolismo , Glândula Tireoide/metabolismo , Tireotropina/metabolismo
17.
J Reprod Immunol ; 25(1): 81-8, 1993 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8271241

RESUMO

Mononuclear cells isolated from liver, spleen and thymus of fetuses between 18 and 24 weeks gestational age were stained for a number of lymphoid cell markers by indirect immunofluorescence and analyzed by flow cytometry. Studies were carried out on freshly isolated mononuclear cell preparations and on cultured cells after selective expansion in interleukin 2 (IL2). Many mononuclear cells in fresh isolates of liver and spleen could not be identified with antibodies to mature T- and B-cell markers. An average of 3% of isolated liver cells and 34% of isolated spleen cells stained positively for CD3, and 19% of liver cells and 37% of spleen cells stained positively for CD20. Lymphoid cells of the fetal thymus were an average 67% CD3+, 76% CD4+, 84% CD8+, and showed greater CD45RO staining (93%) than mononuclear cells of other tissues. Propagation of liver and spleen cell populations in culture favored CD3 phenotypes and CD8 phenotypes. Propagated T cell populations of liver and spleen were primarily TCR alpha/beta+ (81% in liver, 85% in spleen), suggesting a selective advantage in IL2 expansion of alpha/beta T cells over gamma/delta T cells. Propagated gamma/delta T cells of liver and spleen were predominantly TCR gamma/delta 2+. Whereas propagated cells of liver and spleen consisted of approximately 10% gamma/delta+ cells, thymus-derived cells expanded in culture were only an average of 2% TCR gamma/delta+, demonstrating a rarity of IL2-responsive gamma/delta T cells in middle gestation fetal thymus.


Assuntos
Feto/imunologia , Leucócitos Mononucleares/imunologia , Fígado/embriologia , Baço/embriologia , Timo/embriologia , Antígenos CD/análise , Citometria de Fluxo , Imunofluorescência , Idade Gestacional , Humanos , Imunofenotipagem , Interleucina-2/análise , Fígado/citologia , Receptores de Antígenos de Linfócitos T alfa-beta/análise , Receptores de Antígenos de Linfócitos T gama-delta/análise , Baço/citologia , Timo/citologia
18.
J Reprod Immunol ; 25(1): 1-13, 1993 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8271236

RESUMO

In order to characterize the phenotypic composition of populations of lymphoid cells in maternal and fetal tissues during the period of middle gestation, mononuclear cells were isolated from maternal peripheral blood, fetal spleen, fetal thymus and placenta of 18-24 week pregnancies. Peripheral blood and placental isolates were stained for a number of lymphoid cell markers by indirect immunofluorescence and analyzed by flow cytometry. Studies were performed on both freshly isolated mononuclear cell preparations and in vitro cultured cells after selective expansion in interleukin 2 (IL2). Fresh placental mononuclear cell isolates were an average 20% CD3+; their CD4/CD8 ratios varied among individuals. An average of 68% of the lymphocytes isolated from maternal peripheral blood were CD3+. Placental and maternal peripheral blood isolates had comparable percentages of CD16+ and CD20+ cells, while CD56+ cells were present at significantly greater numbers in the lymphocyte compartment of placenta (17%) than in peripheral blood (3%; P < 0.01). Lymphocyte isolates were expanded by culture with IL2 and PHA and stained to determine if propagated lymphocyte populations are representative of initial isolates. Expansion of all lymphocyte isolates favored CD3 phenotypes and CD8 phenotypes. Compared to expanded placenta-derived populations, expanded peripheral blood lymphocytes were similar with regard to percentages of all phenotypes except gamma/delta T cells which represented more of placental lymphocytes (10%) than peripheral lymphocytes (5%; P < 0.01). Surface HLA typing determined propagated placenta-derived lymphocytes to be of maternal and not fetal origin. In vitro propagation of placental mononuclear cell isolates may therefore provide populations of maternal CD3+ lymphocytes for assessment of function and specificity.


Assuntos
Linfócitos/imunologia , Placenta/citologia , Gravidez/imunologia , Antígenos CD/análise , Células Cultivadas , Feminino , Feto/imunologia , Citometria de Fluxo , Antígenos HLA/análise , Humanos , Imunofenotipagem , Placenta/imunologia , Segundo Trimestre da Gravidez , Receptores de Antígenos de Linfócitos T alfa-beta/análise , Receptores de Antígenos de Linfócitos T gama-delta/análise , Baço/citologia , Baço/imunologia , Timo/citologia , Timo/imunologia
19.
Microsc Res Tech ; 37(1): 62-8, 1997 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-9144622

RESUMO

Pulmonary neuroendocrine cell products, especially bombesin-like peptides, are important modulators of fetal lung growth, morphogenesis and maturation. In the present study, we describe the ontogeny of protein gene product 9.5 (PGP 9.5) in 28 midtrimester human fetal lungs, in comparison to chromogranin A (CGA), a marker of differentiated neuroendocrine cells, and proliferating cell nuclear antigen (PCNA), which is expressed by actively dividing cells. PGP 9.5 immunostaining colocalized with CGA in many cells, although the peak abundance of PGP 9.5 preceded that of CGA by 4 to 6 weeks. In addition, a novel staining pattern was noted for PGP 9.5: diffuse cytoplasmic staining of undifferentiated epithelial cells, which was demonstrated by all of the airways before 15 weeks gestation. After gestational week 15, only the smallest airways demonstrated this pattern. PCNA immunostaining demonstrated age-dependent regional variation. All samples had approximately 25% epithelial cells immunopositive for PCNA. Between 11 and 14 weeks gestation over 50% of the mesenchymal cells were PCNA positive. This mesenchymal staining decreased after 14 weeks, and was rare by week 19. There was no definite correlation between the immunostaining for PGP 9.5 and that for PCNA, although PGP 9.5 positive cells were usually PCNA negative. These observations suggest that other growth factors produced by non-neuroendocrine epithelial cells also participate in lung development.


Assuntos
Cromograninas/análise , Pulmão/química , Pulmão/embriologia , Antígeno Nuclear de Célula em Proliferação/análise , Tioléster Hidrolases/análise , Cromogranina A , Feminino , Humanos , Imuno-Histoquímica , Gravidez , Ubiquitina Tiolesterase
20.
Obstet Gynecol ; 57(6): 722-4, 1981 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-6940056

RESUMO

In human corpus luteum (CL) microsomes, danazol inhibited 3 beta-hydroxysteroid dehydrogenase, 17,20-lyase, 17 alpha-hydroxylase, and 17 beta-hydroxysteroid dehydrogenase enzymes. Danazol did not inhibit aromatase. The observation that danazol can directly inhibit multiple enzymes of CL steroidogenesis may provide a molecular basis for explaining previous reports that danazol inhibits CL steroidogenesis in the monkey in vivo.


Assuntos
Corpo Lúteo/metabolismo , Danazol/farmacologia , Hidroxiesteroide Desidrogenases/metabolismo , Pregnadienos/farmacologia , Adulto , Aromatase/metabolismo , Corpo Lúteo/efeitos dos fármacos , Corpo Lúteo/enzimologia , Feminino , Humanos , Hidroxiesteroide Desidrogenases/antagonistas & inibidores , Liases/antagonistas & inibidores , Oxigenases de Função Mista/antagonistas & inibidores
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA