Search PubMed⌕ Search

Biomedical subjects

R B Jaffe

Publications and source records attributed to R B Jaffe.

At least 127 records · Page 7Linked to original sources
PubMed1988

Adrenocorticotropic hormone does not induce desensitization in human adrenal cells during fetal life.

We investigated whether human fetal adrenal cells pretreated with or continuously exposed to adrenocorticotropic hormone (ACTH) would develop refractoriness of the steroidogenic response. Fetal adrenal glands from fetuses of 18-24 wk gestation, were studied. Fetal zone cells were pretreated with increasing doses of ACTH (0-10(-6) M) for 24 h and then restimulated with a single dose of ACTH (10(-6) M) for an additional 24 h. Regardless of the dose of ACTH in the first incubation, the cells responded to the second stimulation with a 2- to 6-fold increase in dehydroepiandrosterone sulfate (DHAS) production. When human fetal adrenal cells were incubated in the continuous presence of 10(-8) M ACTH for 72 h, DHAS production was increased compared to that of the untreated cultures (5-fold at 24 h and 50-fold at 72 h), and the cells remained responsive during the entire experimental period. In contrast, human adult adrenal cells showed a significant decrease of the steroidogenic response after 48 h of ACTH treatment. Twenty-four hours of incubation with increasing doses of ACTH also increased the basal steroidogenic capacity of the fetal adrenal cells. One of the steroidogenic enzymatic steps stimulated by ACTH pretreatment was that of 17 alpha-hydroxylase/17, 20-lyase, since conversion of pregnenolone and 17 alpha-hydroxypregnenolone to DHAS was increased in a dose-dependent manner. These results demonstrate that human fetal adrenal cells, in contrast to those of the adult, do not become desensitized to ACTH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1988

Detection of a potential progenitor cell in the human fetal pituitary that secretes both growth hormone and prolactin.

The structural similarities between human PRL (hPRL) and human GH (hGH) suggest a common evolutionary origin of the two hormones. The existence of these similarities also suggests the existence of a developmental intermediate cell type which has the potential to produce and secrete both hPRL and hGH. We have applied reverse hemolytic plaque assays to monitor the secretions of individual fetal human pituitary cells to determine if any of these cells secrete both hPRL and hGH. When hPRL and hGH assays were performed sequentially on cells obtained from five fetuses of 18-22 weeks gestational age, we consistently found a subpopulation of cells that formed plaques in both assays, i.e. they secreted both hPRL and hGH. The majority of fetal cells secreting hPRL also secreted hGH at this stage of development. These data were corroborated with light and electron microscopic immunocytochemical localization of hPRL and hGH in a subpopulation of previously identified fetal somatotrophs. These findings suggest that in addition to the classical somatotrophs and lactotrophs, the fetal human pituitary contains an additional cell type which secretes both hPRL and hGH. The dual hormone-secreting cell may represent a common progenitor of these classical cell types. It also may be the cell of origin of those pituitary tumors that secrete both PRL and GH.

Cytoplasmic Granules↗
PubMed1988

Effects of growth hormone (GH)-releasing hormone and somatostatin on GH secretion from individual human and monkey fetal anterior pituitary cells: modulation by thyroid hormones and glucocorticoids.

A reverse hemolytic plaque assay was used to measure the GH responses of fetal pituitary cells to GHRH, SRIH, T3 and glucocorticoids. Cells from eight human abortuses (18-22 weeks' gestation) showed accelerated plaque formation after treatment with 10(-7) mol/L GHRH-(1-44) [25.6 +/- 0.6% (+/- SE) of cells formed plaques (PFC); mean area, 14.5 +/- 2.7 X 10(4) micron2; all at 1 h], while 10(-7) mol/L SRIH-(1-28) slowed plaque formation (8.6 +/- 0.6% PFC; mean area, 4.2 +/- 0.8 X 10(4) micron2) vs. control (13.7 +/- 0.7% PFC; mean area, 5.3 +/- 0.8 X 10(4) micron2; all at 1 h). The proportion of PFC was equal in GHRH-treated and control groups by 4 h, suggesting that GHRH affects the amount of GH secreted per somatotroph rather than the number of cells that are preferentially responsive to GHRH. Qualitatively similar data were obtained using pituitary cells from four near-term rhesus fetuses. When cells were cultured in defined medium for 3 days, supplementation with T3 reduced basal GH secretion and attenuated the responses to GHRH. Culture with dexamethasone increased basal GH secretion and restored the responsiveness to GHRH. Dexamethasone also caused a shift in plaque area frequency distributions to patterns similar to those in serum-supplemented medium. We conclude that fetal somatotrophs are responsive to SRIH, GHRH, T3, and dexamethasone. Furthermore, glucocorticoids can maintain a subpopulation of fetal somatotrophs in the GHRH-responsive state.

Animals↗
PubMed1988

Quantitative assessment of the ontogeny of met-enkephalin, norepinephrine and epinephrine in the human fetal adrenal medulla.

The catecholamine producing cells of the adrenal medulla of fetal as well as adult mammals contain enkephalins. We have quantified met-enkephalin and the catecholamines, norepinephrine and epinephrine, in human fetal adrenal glands during the late first trimester and throughout the second trimester of intrauterine life. Met-enkephalin (ME) was detectable in human fetal adrenals of 11 to 25 weeks' gestation by RIA. ME concentrations were low through 14 weeks (mean 279 +/- 199 pg/gland), higher but extremely variable from 15 to 20 weeks (mean 1100 +/- 1000 pg/gland), and then lower with somewhat less variation through 25 weeks (mean 865 +/- 625 pg/gland). In contrast, catecholamine concentrations were below 1100 ng/gland through 16 weeks, then increased markedly by 21 weeks. Approximately equal concentrations of norepinephrine and epinephrine were measured throughout the gestational age period studied. Our data demonstrate that enkephalin is present in the human fetal adrenal at least by 11 weeks' gestation and suggest that the fetal adrenal may be capable of secreting enkephalins as well as catecholamines. The functional significance of adrenal enkephalin secretion remains to be elucidated.

Adrenal Medulla↗
PubMed1987

Regulation of human granulosa-luteal cell progesterone production and proliferation by gonadotropins and growth factors.

The effects of human chorionic gonadotropin (hCG), follicle-stimulating hormone (FSH), fibroblast growth factor (FGF), and epidermal growth factor (EGF) on human granulosa-luteal cell proliferation and progesterone (P) production were studied in vitro. The cells were obtained from an in vitro fertilization protocol and were cultured for 2 to 12 days on plastic culture dishes or on dishes coated with extracellular matrix (ECM). During the first 2 to 4 days of culture, basal P production was high and could not be further stimulated with gonadotropins. Thereafter, basal P production decreased and could be stimulated by both hCG and FSH. The cells growing on ECM produced less P than the cells growing on plastic. EGF and FGF significantly increased cell proliferation on both substrates. FGF did not influence P production, while EGF clearly increased basal P production of the cells cultured on plastic. The high P production in cultured human granulosa cells obtained from follicles stimulated in vivo indicates that at least some of the cells were luteinized. The present data also demonstrate that EGF and FGF are mitogenic for human granulosa-luteal cells, and EGF regulates their biosynthesis in vitro. These results suggest that growth factors may also regulate granulosa cell function in vivo.

Cell Division↗
PubMed1987

Hormonal regulation of messenger ribonucleic acids for P450scc (cholesterol side-chain cleavage enzyme) and P450c17 (17 alpha-hydroxylase/17,20-lyase) in cultured human fetal adrenal cells.

ACTH has acute and long term effects on adrenal steroidogenesis by week 14 of fetal life. We used human fetal adrenal cells to investigate the long term effect of physiological doses of ACTH on mRNAs for P450scc (the cholesterol side-chain cleavage enzyme) and P450c17 (17 alpha-hydroxylase/17,20-lyase). Monolayer cultures of 18- to 24-week gestation fetal zone adrenal cells were maintained in the presence and absence of 10(-9) or 10(-8) M ACTH for up to 12 days. As assessed by RNA dot blots probed with cloned homologous human cDNAs, ACTH increased P450scc and P450c17 mRNAs 4- and 9-fold, respectively, over control values on day 7 of culture. ACTH-mediated stimulation was slightly less on day 12 of culture. The ACTH-mediated accumulation of those mRNAs were time dependent. When cells were exposed to a single 10(-8)-M dose of ACTH, the amount of P450scc and P450c17 mRNA was increased by 24 h, reaching a maximum at 48 h and diminishing by 72 h. When cells were maintained in 10(-8) M ACTH continuously, mRNA for both enzymes accumulated in a similar pattern, reaching a peak at 48 h but remaining at nearly maximal values thereafter, up to 96 h. Dibutyryl cAMP (10(-3) M) mimicked these stimulatory actions of ACTH, although its effect was greater at 24 h and more stable up to 96 h. Angiotensin II (1-100 ng/mL) and hCG (1-100 ng/mL) had no effect on accumulation of P450scc and P450c17 mRNAs. The production of both dehydroepiandrosterone sulfate and cortisol also was stimulated by ACTH, suggesting that the increased mRNAs were translated into active enzymes. These results indicate that ACTH induces human fetal adrenal cells to accumulate mRNAs for both P450scc and P450c17; this effect of ACTH is probably mediated by cAMP. Chronic 96-h stimulation of human fetal adrenal cells did not diminish their responsiveness to ACTH. Together with our earlier studies of the human fetal adrenal, these data indicate that fetal adrenal tissue does not exhibit the desensitization to trophic hormone stimulation characteristic of adult tissue.

Adrenal Glands↗
PubMed1987

Estradiol sensitization of cultured human fetal pituitary cells to gonadotropin-releasing hormone.

In adult women, estradiol (E2) sensitizes the pituitary to GnRH. To assess whether this effect develops during intrauterine life, dispersed pituitary cells from second trimester male and female fetuses were cultured on extracellular matrix-coated plates. E2 (10(-8) mol/L) exposure for 72 h resulted in a significant increase in LH release when cells were stimulated with GnRH and caused a significant shift to the left of the dose-response curve for GnRH-stimulated LH release [relative potency ratio, 0.33 +/- 0.05 (+/- SE)]. E2-enhanced LH release was not associated with an increase in cell number, total LH content, or percentage of LH-containing cells (immunocytochemistry). The EC50 of GnRH-stimulated LH release and the degree of E2 sensitization were not sex dependent, although female fetal pituitary cells in the absence of E2 had significantly greater LH content and released more LH under basal and GnRH-stimulated conditions than cells from male fetuses. Therefore, E2 sensitization of second trimester human fetal gonadotrophs to GnRH does occur, is not influenced by sex, and may involve an acutely releasable LH pool. At these gestational ages, basal and maximal GnRH-stimulated LH release as well as total LH content are greater in the female than the male. Thus, E2 sensitization of GnRH responsiveness appears to have its origins during intrauterine fetal life.

Drug Synergism↗
PubMed1987

Follicle-stimulating hormone receptors appear earlier in the primate fetal testis than in the ovary.

Receptors for FSH as well as FSH-stimulated cAMP production were measured in gonadal tissue of human fetuses of 8-16 weeks gestation and of rhesus monkey fetuses in the last third of gestation. A single population of high affinity receptors (Ka, 1.5-4 X 10(9) M-1) for human FSH was detected in testicular tissue of both species. Specific FSH binding was absent in the human ovaries but present in the two monkey fetal ovaries studied. FSH (1 microgram/mL) did not stimulate cAMP production in slices of any of the gonads studied (human fetal testes and monkey fetal testes and ovaries) or in cultured human granulosaluteal cells used in a control experiment, but FSH increased cAMP 10-fold in immature (10-day-old) rat testes. We conclude that the primate fetal testis, both during the first half and at the end of gestation, may be responsive to FSH stimulation, although this response does not involve the acute elevation of cAMP. In contrast, the absence of FSH receptors in early and midterm human fetal ovaries and the presence of such binding in this tissue in the late gestation monkey indicate that the ovary becomes responsive to FSH stimulation during later stages of fetal development.

Aged↗
PubMed1987

Therapeutic uses of gonadotropin-releasing hormone analogs.

Since the discovery and synthesis of gonadotropin-releasing hormone (GnRH) in 1971, numerous long-acting agonistic and antagonistic analogs have been synthesized. Agonistic analogs were found to desensitize pituitary GnRH receptors with chronic use, resulting in decreased gonadotropin secretion and a hypogonadal state. These analogs are being investigated as potential contraceptives and in the treatment of several conditions in which decreased gonadal steroid production is desired. Substantial progress has been made in these areas. The purpose of this review is to provide the clinician with data regarding the potential clinical utility of this class of peptides.

Contraceptive Agents, Female↗
PubMed1986

Corticotropin-releasing factor can stimulate gonadotropin secretion by human fetal pituitaries in superfusion.

In previous studies, corticotropin-releasing factor was found to elicit a rise in circulating adrenocorticotropic hormone in human subjects and laboratory animals, but no stimulatory effect of corticotropin-releasing factor on other pituitary hormones was detected. Since stress may be associated with luteinizing hormone changes as well as with those of corticotropin-releasing factor and adrenocorticotropic hormone, we quantified gonadotropin responses to corticotropin-releasing factor and arginine vasopressin in 11 human fetal pituitaries with use of both superfusions and static incubations. Exposure to corticotropin-releasing factor brought about a significant increase in adrenocorticotropic hormone and gonadotropin concentrations in the effluent media by means of the superfusion system. Similar concentrations of corticotropin-releasing factor significantly increased adrenocorticotropic hormone secretion into the medium by dispersed fetal pituitary cells cultured on an extracellular matrix but failed to increase luteinizing hormone and follicle-stimulating hormone secretion. Exposure to 3 mmol/l 8-bromo-cyclic adenosine monophosphate caused an increase in all three peptides, both in superfusion and static incubations. Dose-response studies showed that the effect on gonadotropin secretion occurred at concentrations of 8-bromo-cyclic adenosine monophosphate two orders of magnitude lower than those affecting adrenocorticotropic hormone secretion. The purity of corticotropin-releasing factor and arginine vasopressin used in these studies was confirmed by high-performance liquid chromatography. These in vitro results are consistent with a paracrine effect of corticotropes acting on gonadotropes. The combination of static incubation and superfusion has proved useful in elucidating the effects of different secretagogues on pituitary cells.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1986

Induction of ovulation in the postpartum rhesus monkey: factors determining success in obtaining primate luteal tissue.

Ovulation induction in the postpartum rhesus monkey was attempted with the use of purified human pituitary gonadotropins for assessment of (1) whether this procedure could be used to provide a source of luteal tissue; (2) the extent of ovarian responsiveness to gonadotropic stimulation; (3) factors that might facilitate ovulation induction during the peurperium; and (4) factors that might be a contributory cause of induction failure. Twenty rhesus monkeys were treated with purified human follicle-stimulating hormone (hFSH) and human luteinizing hormone (hLH) twice daily, beginning on days 0, 10, or 20 postpartum, with or without prior administration of bromocriptine. Laparotomies were performed during the midluteal phase. Ovaries were examined, and all corpora lutea were removed. Neither the day of beginning the gonadotropin treatment nor bromocriptine administration had a significant effect on the success rate of ovulation induction, which averaged 60% overall. Inductions begun during July had a significantly (P less than 0.025) lower success rate than those started at other times of the year. Antibodies to hFSH and hLH were detected in serum from monkeys that had undergone ovulation induction. Antibodies to hFSH, but not hLH, were associated with significantly reduced induction success (P less than 0.05). Plasma estradiol rose in response to gonadotropin treatment, and the induced follicular phase averaged 13.6 +/- 0.7 days. In all animals judged to have ovulated, corpora lutea were observed at laparotomy, and plasma concentrations of progesterone were significantly elevated (13.8 +/- 3.8 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Uterine leiomyomas: correlation of MR, histopathologic findings, and symptoms.

Magnetic resonance (MR) imaging, symptoms, and pathologic findings were correlated in 59 uterine leiomyomas from 23 patients. The tumors varied from less than 1 cm to 18 cm in diameter. Fifty-seven leiomyomas were identified in the corpus uterus, one was located within the broad ligament, and another was detected in the cervix. Among the corpus lesions, 9 were correctly identified on MR images as subserosal and 37 as intramural. Of 11 tumors assigned at surgery to the submucosal group, 10 had been accurately defined with MR. On MR, myomas associated with hypermenorrhea produced an anatomic disruption of the "junctional zone" (the low-intensity band seen at the myometrium-endometrium junction on T2 contrast images). Long TR (2 sec) and TE (56 msec) parameters (T2 contrast images) yielded the best contrast resolution between leiomyoma and surrounding myometrium. Correlation of MR with histologic features demonstrated 2 groups of lesions. Leiomyomas free of degenerative changes emitted homogeneous signals of low intensity. Contrast between tumor and myometrium was -16% on the T1 contrast image and increased to -44 +/- 16% on the T2 contrast image. Leiomyomas with hyaline, myxomatous, or fatty degeneration demonstrated various degrees of inhomogeneity, best seen on images obtained with long TR and TE. It is concluded that MR is an accurate modality for imaging uterine leiomyomas, since it clearly demonstrates tumor number, size, location, and the presence and extent of degeneration.

Adipose Tissue↗
PubMed1986

Uterine MR imaging: effects of hormonal stimulation.

Magnetic resonance (MR) imaging characteristics of the uterine corpus were evaluated in 40 women divided into five physiologic categories (nine premenarchal, 13 reproductive age not taking hormones, seven reproductive age taking oral contraceptives, six reproductive age taking gonadotropin releasing hormone analog, and five postmenopausal). Images were generated using a 0.35-T magnet and a double spin-echo technique. On both T1-weighted and T2-weighted images, premenarchal and postmenopausal uteri were small and relatively featureless. Uteri on T2-weighted images in reproductive age women not taking exogenous hormones showed variations in endometrial and myometrial width, signal intensity, and T1 and T2 values during the menstrual cycle. Oral contraceptives and gonadotropin releasing hormone analogs caused endometrial atrophy and alterations in myometrial signal intensity and T1 and T2 values. A detailed gynecologic history is therefore essential in the evaluation of uterine anatomy in patients undergoing pelvic MR imaging.

Atrophy↗
PubMed1986

Inadvertent ligation of the left pulmonary artery.

In five patients, aged 4 days to 20 months, the left pulmonary artery was inadvertently ligated at the time of attempted closure of the patent ductus arteriosus. The complication was recognized in these patients between 1 day and 5 years later from findings of chest radiography, two-dimensional echocardiography with spectral analysis of Doppler shifted echoes, and angiography. In three patients, the presence of asymmetric pulmonary blood flow on chest radiographs obtained after surgery initially suggested the diagnosis. In the other two patients with bronchopulmonary dysplasia, the diagnosis was made by means of two-dimensional echocardiography and Doppler spectra in one and angiography in the other. On angiograms, the left pulmonary artery distal to the ligation was visualized by delayed opacification from aortic collaterals in three patients and by means of pulmonary venous wedge injection in one. Radiographic and echocardiographic examination with Doppler spectra may permit prompt diagnosis and early correction of this complication.

Ductus Arteriosus, Patent↗
PubMed1986

Hypophysiotropic and neuromodulatory regulation of adrenocorticotropin in the human fetal pituitary gland.

Synthetic human corticotropin-releasing factor (hCRF) stimulated ACTH secretion by human fetal pituitaries in superfusion and dispersed human fetal pituitary cells cultured on an extracellular matrix in static incubation from 14 to 23 wk gestational age. The action of hCRF in vitro was potentiated by arginine vasopressin (AVP) at all ages studied. 8-Br-cAMP induced a response similar to hCRF. The AVP effect on ACTH was synergistic with both CRF and 8-Br-cAMP. hCRF-mediated secretion of ACTH was noncompetitively inhibited by 24-h pretreatment, or by 3-h concomitant treatment, with dexamethasone. Neither oxytocin, catecholamines, prostaglandins, nor indomethacin exerted significant effects on ACTH secretion, either alone or in combination with hCRF or AVP during the gestational ages studied. These results support a physiologic role for CRF in the regulation of secretion by corticotropic cells as early as 14 wk gestation, by which time corticotropes and ability to secrete ACTH have been demonstrated.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1986

Persistence of fetal zone function in the infant rhesus monkey adrenal gland.

Plasma dehydroepiandrosterone sulfate (DHAS) concentrations increase markedly in the rhesus monkey fetus at the end of gestation. A further increase occurs in the infant. To determine whether the changes in plasma concentration between the fetus and infant represent maintenance of DHAS production by the infant adrenal gland, we measured the t1/2, distribution volume (VD), MCR, and production rate of DHAS in the late gestation rhesus monkey fetus (129-155 days gestation; term is 165 days) and infant (14-42 days of age). A single bolus dose of [3H]DHAS was injected into five fetuses and four infants, and blood samples were collected serially from 5 min to 24 h after the injection. The amount of [3H]DHAS in the circulation was measured after solvolysis, extraction, and Celite chromatography. The concentration of DHAS in each sample was measured by RIA. DHAS was cleared significantly more rapidly in the fetus than in the infant [MCR in fetus, 2.4 +/- 0.4 (+/- SE); MCR in infant, 0.6 +/- 0.2 liters day-1 kg-1]. The t1/2 of DHAS was shorter in the fetus than in the infant (1.0 +/- 0.1 vs. 3.3 +/- 0.7 h). Absolute VD values were larger in the fetus than in the infant (231 +/- 29 and 143.8 +/- 11.6 ml kg-1); however, they were similar when the fetal VD was calculated including placental weight as a component of fetal weight. The production rate of DHAS, calculated as the product of MCR and integrated plasma DHAS concentration for the duration of the experiment, was not significantly different between the fetus and the infant (1.0 +/- 0.2 and 3.3 +/- 1.2 mg kg-1 day-1) in spite of the marked differences in plasma DHAS concentrations (445.8 +/- 103.8 ng ml-1 in the fetus and 5165 +/- 1296 ng ml-1 in the infant). These results indicate that the adrenal of the infant rhesus monkey continues to secrete DHAS at a rate at least as high as that in the late gestation fetus. Since the infant maintains DHAS production similar to that of the fetus in the absence of the placenta, a corollary of these studies is that the elevated DHAS secretion in the rhesus infant is independent of the placenta or the hormonal milieu of pregnancy. The maintenance of a functional fetal zone in the adrenal gland makes the rhesus infant a suitable model to use in studying the regulation of DHAS secretion and fetal zone morphology.

Adrenal Glands↗