Biomedical subjects

J J Chen

Publications and source records attributed to J J Chen.

At least 19 recordsLinked to original sources

PubMed1999

Regulation of testosterone secretion by prolactin in male rats.

The goal of this study was to characterize the mechanism by which hyperprolactinemia alters testosterone production in rat testicular interstitial cells (TICs). Hyperprolactinemia was induced by grafting 2 anterior pituitary (AP) glands under the subcapsular space of the kidney in experimental rats. Control rats were grafted with brain cortex (CX). Six weeks post-grafting, rats were challenged with human chorionic gonadotropin (hCG) then, the changes in either plasma testosterone or luteinizing hormone was measured. Additionally, TICs were isolated and challenged in vitro with hCG or prolactin, and the testosterone release measured by radioimmunoassay. Further investigation in signal transduction as intracellular 3':5' cyclic adenosine monophosphate (cAMP) production was observed under a regulation of forskolin or SQ22536. After the challenge of hCG or GnRH, the AP-grafted rats showed a suppressed response in testosterone release as compared to those in the CX-grafted group. The in vitro data from the AP-grafted rats compared to the CX-grafted animals showed a diminished response in testosterone release upon hCG stimulation. Administration of forskolin or SQ22536 disclosed dysfunction of adenylate cyclase in TICs from the AP-grafted rats. When 8-Br-cAMP was incubated with TICs, the testosterone production was lower in the AP-grafted compared to the CX-grafted group. These results suggest that in addition to adenylate cyclase dysfunction, inefficiency of post-cAMP pathways are also involved in the hypogonadism elicited by hyperprolactinemia in rats.

Animals↗

PubMed1999

Ethanol, oxidative stress, reactive aldehydes, and the fetus.

The fetotoxic effects of maternal ethanol (E) consumption have been documented for over two decades, yet the mechanisms underlying this devastating phenomenon remain uncertain. The wide variety of cellular/biochemical effects of E on fetal tissues is itself a puzzle and strongly suggests that fetotoxic responses to E reflect a multifactorial setting. Many of these responses can be conceptually connected to effects on membrane structure and function. Representative of this, are studies in our laboratory documenting E effects on fetal cell replication, membrane transport systems, membrane fluidity, Na+-K+ pump expression, and EGF receptor expression. Recent studies have provided evidence that oxidative stress may be one mechanism by which E produces these membrane-related events. We initially observed E-induced oxidative stress in cultured fetal rat hepatocytes, the latter exhibiting morphological and biochemical signs of mitochondrial damage. E increased H2O2, O2-, lipid peroxidation products, along with signs of membrane damage. Supplementation with antioxidants or agents that enhance glutathione stores reversed these effects. E was found to inhibit activities of mitochondrial respiratory chain components (a potential source of the enhanced levels of H2O2, and O2-) and this could be reversed by antioxidant treatment. Subsequent studies have documented oxidative stress and membrane lipid peroxidation in fetal brain and liver (gestation day 19) following a two day maternal E consumption and in gestation day 14 and 17 "embryos" immediately following a single dose of E to the pregnant dam. The means by which E can induce oxidative stress in fetal cells is under investigation. We have examined effects of E on activities of key antioxidant enzymes and found no depressant responses. However, the low levels of antioxidants in fetal tissues and an exaggerated response of fetal mitochondria to prooxidant stimulation in vitro, suggest that fetal cells are strongly predisposed to oxidative stress. Additionally, recent studies have suggested that fetal tissues are likewise prone to the formation and subsequent accumulation of at least one toxic lipid peroxidation product, 4-hydroxynonenal. We conclude that maternal E consumption induces oxidative stress in fetal tissues and that this is responsible for some toxic responses to E. Additionally, the low antioxidant defenses in fetal tissues and accumulation of toxic aldehyde products of lipid peroxidation predispose the fetus to oxidative damage.

Aldehydes↗

PubMed1999

Analysis of drug dissolution data.

Drug absorption in the human body depends on the dissolution rate of the drug. Suitable dissolution characteristics are important to ensure that the drug will achieve the desired therapeutic effects. To assess the similarity of dissolution rates of several drug lots, we apply a general growth curve model with different covariance structures. The Box-Cox power transformation and the naive log transformation are applied to a function of the dissolution rate. The predictive sample-reuse, or cross-validation, method is employed in selecting an appropriate model with best predictive accuracy. A testing procedure for examining the similarity among the drug lots is also conducted. A partially Bayesian approach is used for the assessment of dissolution equivalence.

Bayes Theorem↗

PubMed1999

Upregulation of protein synthesis initiation factor eIF-4E is an early event during colon carcinogenesis.

A general increase in protein synthesis and a specific increase in the synthesis of growth-promoting proteins are necessary for mitogenesis. Regulation of protein synthesis, as well as preferential translation of some mRNAs coding for growth promoting proteins (e.g. cyclin D1), involves the essential protein synthesis initiation factor eIF-4E. This factor is induced by various oncoproteins, and, when overexpressed, it can transform cultured cells. In this report we explore the roles of eIF-4E in human neoplastic disorders of the colon and in the regulation of general and specific protein synthesis. We find that eIF-4E is increased in colon adenomas and carcinomas, and this increase is accompanied in most but not all cases by elevation of cyclin D1 levels. While general protein synthesis is increased by eIF-4E overexpression in cultured cells, only a small proportion of proteins is preferentially upregulated by eIF-4E, as revealed by two-dimensional gel electrophoresis. These results are consistent with the view that eIF-4E plays a role in carcinogenesis by increasing general protein synthesis and by preferentially upregulating a subset of putative growth promoting proteins. Our results, taken together with the recent findings that c-myc transcription is negatively regulated by APC and our earlier data on transcriptional activation of eIF-4E expression by c-Myc suggest that eIF-4E is a downstream target of the APC/beta-catenin/Tcf-4 pathway, and is strongly involved in colon tumorigenesis.

3T3 Cells↗

PubMed1999

Effects of estradiol on aldosterone secretion in ovariectomized rats.

The effects and action mechanisms of estradiol on aldosterone secretion in female rats were studied. Replacement of estradiol benzoate (EB) increased the levels of plasma estradiol and aldosterone in ovariectomized (Ovx) rats. The aldosterone release from zona glomerulosa (ZG) cells was higher in EB-treated rats than in oil-treated animals. EB treatment potentiated the responses of aldosterone release to adrenocorticotropic hormone (ACTH), forskolin (FSK), and 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP). Administration of EB in vivo did not alter cAMP production in response to ACTH or FSK. Although angiotensin II (Ang II) increased aldosterone secretion by rat ZG cells, the stimulatory effect of Ang II on the release of aldosterone was not altered by EB treatment. The conversions of [3H]-deoxycorticosterone to [3H]-corticosterone and [3H]-corticosterone to [3H]-aldosterone in EB-treated groups were greater than those in the oil-treated group. These results suggest that estradiol increases aldosterone secretion in part through the mechanisms involving the activation of the post-cAMP pathway, 11beta-hydroxylase and aldosterone synthase activity.

Adrenocorticotropic Hormone↗

PubMed1999

BRCA1, BRCA2, and Rad51 operate in a common DNA damage response pathway.

The two major hereditary breast cancer susceptibility genes, BRCA1 and BRCA2, are associated with early-onset breast and/or ovarian cancer and encode products that each interact with the product of the eukaryotic RecA homologue, hRad51. We have recently found that BRCA1 and BRCA2 coexist in a common biochemical complex. The two proteins also colocalize in subnuclear foci in somatic cells as well as on the axial elements of developing synaptonemal complexes in meiotic cells. Thus, BRCA1 and BRCA2 participate in a common DNA damage response pathway associated with the activation of homologous recombination and double-strand break repair. Dysfunction of this pathway may be a general phenomenon in the majority of cases of hereditary breast and/or ovarian cancer. The BRCA1/BRCA2 complex may function in postreplicational repair processes activated during the DNA synthesis stage of the cell cycle.

BRCA2 Protein↗

PubMed1999

Effects of prolactin on aldosterone secretion in rat zona glomerulosa cells.

Acute effects and action mechanisms of prolactin (PRL) on aldosterone secretion in zona glomerulosa (ZG) cells were investigated in ovariectomized rats. Administration of ovine PRL (oPRL) increased aldosterone secretion in a dose-dependent manner. Incubation of [3H]-pregnenolone combined with oPRL increased the production of [3H]-aldosterone and [3H]-deoxycorticosterone but decreased the accumulation of [3H]-corticosterone. Administration of oPRL produced a marked increase of adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in ZG cells. The stimulatory effect of oPRL on aldosterone secretion was attenuated by the administration of angiotensin II (Ang II) and high potassium. The Ca2+ chelator, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA, 10(-2) M), inhibited the basal release of aldosterone and completely suppressed the stimulatory effects of oPRL on aldosterone secretion. The stimulatory effects of oPRL on aldosterone secretion were attenuated by the administration of nifedipine (L-type Ca2+ channel blocker) and tetrandrine (T-type Ca2+ channel blocker). These data suggest that the increase of aldosterone secretion by oPRL is in part due to (1) the increase of cAMP production, (2) the activation of both L- and T-type Ca2+ channels, and (3) the activation of 21-hydroxylase and aldosterone synthase in rat ZG cells.

3-Hydroxysteroid Dehydrogenases↗

PubMed1999

Aflatoxin B1-induced Hprt mutations in splenic lymphocytes of Fischer 344 rats. Results of an intermittent feeding trial.

In a previous study, we found an increase in the mutant frequency at the Hypoxanthine phosphoribosyl transferase (Hprt) locus in the splenic lymphocytes of Fischer 344 rats acutely exposed to aflatoxin B1 (AFB1). Because an acute exposure may not reflect the exposure pattern of individuals whose diet may contain AFB1-contaminated foodstuffs, we sought to determine if the feeding regimen affected the induction of Hprt mutations in the rat splenic lymphocyte. Thus, Fischer 344 rats were fed either (A) a control diet, (B) various doses of AFB1 for three four-week periods interspersed with two four-week periods of the control diet, or (C) continuously fed 1.6 ppm of AFB1. Not only was a significant increase in the mutant frequency detected in the lymphocytes of rats fed a dose as low as 0. 01 ppm of AFB1, but the increase in the mutant frequency at the end of the 20-week experimental period was consistent with an accumulation of damage induced by AFB1. These results indicate that the rat lymphocyte/Hprt assay is useful for detecting chronic low level exposures. Further, these data suggest that an intermittent, low-level exposure to AFB1 may present a human health risk.

Administration, Oral↗

PubMed1999

The bovine papillomavirus type 1 E6 oncoprotein sensitizes cells to tumor necrosis factor alpha-induced apoptosis.

Expression of viral proteins may result in susceptibility of cells to the cytotoxic effect of Tumor Necrosis Factor Alpha (TNF). While murine C127 cells containing the bovine papillomavirus type 1 (BPV-1) genome were reported to exhibit increased TNF sensitivity, the gene(s) responsible was not identified. The BPV-1 E6 oncoprotein induces tumorigenic transformation of murine C127 cells and stimulates transcription when targeted to a promoter. BPV-1 E6 was introduced into C127 cells (PBE6) by retroviral infection and stable clones were isolated. These cells showed increased apoptosis in response to TNF, as measured by several criteria. TNF-induced apoptosis in PBE6 cells was accompanied by increased release of arachidonic acid, indicating that phospholipase A2 was activated. We also provide evidence that BPV-1 E6 mediated-sensitization of cells to TNF-induced apoptosis can occur in the absence of p53.

Animals↗

PubMed1999

A novel mechanism of CD4 lymphocyte depletion involves effects of HIV on resting lymphocytes: induction of lymph node homing and apoptosis upon secondary signaling through homing receptors.

Recently, we reported that abortive HIV infection of resting human T lymphocytes up-regulated expression of CD62L, the receptor for homing to lymph nodes (LNs), and enhanced homing of these cells from the blood into the LNs (Wang et al., 1997, Virology 228:141). This suggested that HIV-induced homing of resting lymphocytes (which comprise >98% of all lymphocytes) may be a major mechanism for the reduction of CD4+ lymphocytes in the blood of infected individuals. This mechanism also could be partially responsible for the lymphadenopathy that often develops at the same time that CD4+ lymphocytes are disappearing from the blood. In this study, we show that secondary signaling through the homing receptors (CD62L, CD44, CD11a) of abortively infected resting CD4+ T lymphocytes induced apoptosis. These signals would occur as the cells home into the LNs. Apoptosis did not occur after secondary signaling through some other receptors (CD26, CD4, CD45, and HLA class I) or in HIV-exposed resting CD8+ lymphocytes signaled through the homing receptors. These findings indicate that HIV-induced homing of resting CD4+ lymphocytes to LNs results in death of many of these cells. This was confirmed in the LNs of SCID mice that were i.v. injected with HIV-exposed resting human lymphocytes. Thus, these effects of HIV upon binding to resting CD4+ T lymphocytes, which are not permissive for HIV replication, may significantly contribute to their depletion in vivo. These findings also offer an explanation for the bystander effect observed in the LNs of AIDS patients, whereby cells not making virus are dying.

Animals↗

PubMed1999

Multielectrode surface EMG for noninvasive estimation of motor unit size.

To noninvasively estimate the motor unit size, we present a novel surface electromyographic (EMG) measurement system consisting of a surface multielectrode with four-pin electrodes and a pair of surface-disk electrodes. Surface motor unit action potentials (MUAPs) were recorded with the multielectrode, in the so-called multielectrode surface EMG (MSEMG), which was spatially filtered to localize the sensing area and reduce the noise. In addition, a modified decomposition algorithm, considering the geometrical configuration of the multielectrode, was designed to identify the individual MUAPs in the measured MSEMG. The identified MUAP was subsequently used as the triggering source for the EMG signals recorded by the surface-disk electrodes. From a pool of 34 subjects with neuromuscular diseases and 14 normal subjects, the median amplitudes of surface-disk EMG after spike-triggered averaging, called MSEMG-MUAP, correlated well (r = 0.82, P < 0.0001) with those of macro EMG. Moreover, the MSEMG-MUAP recording during a ramp force contraction exhibited the common size principle phenomenon during motor unit recruitment. The results of this study demonstrate that the MSEMG-MUAP measurement is a feasible approach for estimating the motor unit size from the skin surface.

Adolescent↗

PubMed1999

Monitoring catalytic reaction of bilirubin oxidase and determination of bilirubin and bilirubin oxidase activity by capillary electrophoresis.

Micellar electrokinetic chromatography (MEKC) has been exploited as an analytical method for the separation as well as for the determination of serum bilirubin fractions (alpha-, beta-, gamma- and delta-fraction), the activity of bilirubin oxidase (BOD), and for monitoring the catalytic reaction of BOD. The samples were followed by detection at 450 nm. The average limit of detection was in the 5.0 microM concentration range. The relative standard deviation (RSD) of migration times and peak area of bilirubin was less than 0.25% and 3.0%, respectively. This allowed us complete separation of the four bilirubin fractions (alpha-, beta-, gamma- and delta-fraction) and monitoring of the oxidation progress and the assay of the activity of bilirubin oxidase. The MEKC method is a convenient technique for studying the catalytic reaction of bilirubin oxidase at different pH and assaying the relationship between the four bilirubin fractions and diseases.

Bilirubin↗

PubMed1999

Tumor necrosis factor a microsatellite polymorphism is associated with rheumatoid arthritis severity through an interaction with the HLA-DRB1 shared epitope.

OBJECTIVE: To determine whether tumor necrosis factor microsatellite a (TNFa) polymorphism is associated with severity of rheumatoid arthritis (RA), and to examine the evidence for interaction between TNFa and the HLA-DRB1 shared epitope (SE). METHODS: One hundred seventy-one community-based white female RA patients were genotyped for both TNFa and HLA-DRB1 alleles. We performed pairwise association analyses, stratified analyses, and multivariate logistic regressions to determine whether TNFa was associated with 4 measures of RA severity, and whether there was significant interaction between TNFa and the HLA-DRB1 SE. RESULTS: Simple pairwise analyses did not reveal significant association between TNFa polymorphism and RA severity. However, when the data were stratified by the presence versus absence of the SE, striking associations were observed between TNFa allele 11 (TNFa11) and RA severity. These analyses also demonstrated significant interaction between TNFa11 and the SE (P = 0.07-0.005), and this was confirmed in our multivariate regressions. Specifically, the most severe outcomes were observed among individuals who had inherited both TNFa11 and the SE (61-71% had severe RA based on 1 of the 4 outcomes). In contrast, individuals who had inherited TNFa11 in the absence of the SE had the best outcomes (8-21% with severe RA). The odds ratios comparing these 2 groups ranged from 8.8 to 22.7 for the 4 severity measures. The differential effect of TNFa11 according to the presence versus absence of the SE (and vice versa) illustrated their interaction with respect to RA severity. CONCLUSION: The data suggest that TNFa is associated with RA severity through an interaction with the HLA-DRB1 SE.

Adult↗

PubMed1999

A unified approach to risk assessment for cancer and noncancer endpoints based on benchmark doses and uncertainty/safety factors.

A fundamental goal of toxicology is to determine safe levels of human exposure to toxic substances. In the absence of information to establish dose-response relationships at low exposure levels generally experienced by humans, high-dose to low-dose linear extrapolation is generally used for estimating carcinogenic risks and the no-observed-adverse-effect-level divided by uncertainty (safety) factors is widely used for establishing human exposure guidelines for noncancer effects. The basis and impact of this dichotomy is examined and questioned. It is proposed that a unified approach be adopted for establishing human exposure guidelines for both cancer and noncancer endpoints. It is suggested that a lower confidence limit on the dose estimated to produce an excess incidence of adverse health effects in 10% of the individuals in a human study or 10% of the animals in laboratory experiments be used as a point-of-departure. This dose would be divided by appropriate uncertainty factors to establish human exposure guidelines. For severe irreversible adverse health effects we suggest a total default uncertainty factor (divisor) for animal data on the order of 10,000, which is comparable to current guidelines. For reversible biological effects a smaller default uncertainty factor on the order of 1000 may be employed. This is comparable to the divisor often used currently when the point-of-departure is the lowest-observed-adverse-effect-level. It is asserted that the toxicological information generally available does not warrant numerical estimates of risk at low levels of human exposure. Rather, we support a unified approach for all adverse health effects of dividing a benchmark dose by appropriate uncertainty factors to establish guidelines for human exposures to toxic substances.

Benchmarking↗

PubMed1999

Characterization of the rat adrenal medulla cultured in vitro.

A wide variety of experimental animal models have been used to investigate the mechanisms of synthesis, storage, and release of catecholamines. Whereas in vivo experimental models are situated at one end of the spectrum, cell culture models are situated at the other end. In the present study, we have characterized various aspects of the rat adrenal medulla cultured in vitro as a whole tissue, aiming to establish a new experimental model in between in vivo animal models and cell culture models. We adapted a bottle rotator system commonly used for culturing rodent whole embryos. Changes in histology, activities and mRNA levels of catecholamine-synthesizing enzymes, and concentrations of catecholamines in the adrenal medulla were studied. In addition, the effects of cholinergic stimulation on catecholamine release from the adrenal medulla were examined. Overall the results indicate that various aspects of the adrenal medulla become stable after 4 d of culture and the adrenal medulla at this stage releases catecholamines in response to cholinergic stimulation. The whole adrenal medulla culture system may be a useful tool for investigating catecholamine-related functions dependent on intercellular reactions or communications.

Adrenal Cortex Hormones↗

PubMed1999

Expression of the eukaryotic translation initiation factors 4E and 2alpha in non-Hodgkin's lymphomas.

Transition of cells from quiescence to proliferation requires an increase in the rate of protein synthesis, which is regulated in part by two key translation initiation factors, 4E and 2alpha. The expression and activity of both factors are increased transiently when normal resting cells are stimulated to proliferate. They are constitutively elevated in oncogene transformed cultured cells, and overexpression of either initiation factor in rodent cells makes them tumorigenic. In this study we investigate an association between the expression of translation initiation factors and lymphomagenesis. We have analyzed the expression of the protein synthesis initiation factors 4E and 2alpha by immunohistochemistry in reactive lymph nodes and several types of non-Hodgkin's lymphoma representing a wide range of clinical behaviors based on the Revised European-American Lymphoma behavioral classification. The study included 7 benign lymph nodes with follicular hyperplasia, 26 indolent lymphomas (6 marginal zone lymphomas, 7 small lymphocytic lymphomas, and 13 follicular lymphomas, grades 1 and 2), 16 moderately aggressive lymphomas (8 mantle cell lymphomas and 8 follicular lymphomas, grade 3), 24 aggressive lymphomas (14 large-B-cell lymphomas and 10 anaplastic large-cell lymphomas), and 15 highly aggressive lymphomas (7 lymphoblastic lymphomas and 8 Burkitt's lymphomas). Strong expression of initiation factors 4E and 2alpha was demonstrated in the germinal centers of reactive follicles. Minimal or no expression was seen in the mantle zones and surrounding paracortices, indicating that high expression of initiation factors 4E and 2alpha is associated with the active proliferation of lymphocytes. Most cases of aggressive and highly aggressive lymphomas showed strong expression of initiation factors 4E and 2alpha, in contrast to the cases of indolent and moderately aggressive lymphoma, in which their expression was intermediate between the germinal centers and the mantles of reactive follicles. A positive correlation was found between the expression of both initiation factors 4E and 2alpha and the Revised European-American Lymphoma behavior classification (P < 0.05). Thus, constitutively increased expression of initiation factors 4E and 2alpha may play an important role in the development of lymphomas and is correlated with their biological aggressiveness.

Blotting, Western↗

PubMed1999

Reactive oxygen species modulate endothelin-I-induced c-fos gene expression in cardiomyocytes.

OBJECTIVES: Recent evidence indicates that reactive oxygen species (ROS) may act as second messengers in receptor-mediated signaling pathways. The possible role of ROS during Et-1 stimulation in cardiomyocytes was therefore investigated. METHODS: Intracellular ROS levels were measured with fluorescence probe 2',7'-dichlorofluorescin diacetate by confocal microscopy in cultured neonatal rat cardiomyocytes. The ROS-inducible c-fos expression was analyzed by Northern blotting and promoter activity. RESULTS: Et-1 applied to cardiomyocytes dose-dependently increased intracellular ROS levels. The increase of ROS levels was attenuated by pretreating cardiomyocytes with Et-A receptor antagonist-BQ485, but not with Et-B receptor antagonist. Cardiomyocytes pretreated with catalase or an antioxidant N-acetylcysteine (NAC) reduced Et-1-induced ROS levels. Et-1 or H2O2 treatment of cardiomyocytes rapidly induced the expression of an immediate early gene c-fos. Et-1-treated cardiomyocytes enhanced the c-fos gene expression as revealed by functional analysis using a reporter gene construct containing c-fos promoter region (-2.25 kb) and reporter gene chloramphenicol acetyltransferase. The induction of mRNA levels and the promoter activities of c-fos gene by Et-1 or H2O2 were abolished by pretreating cardiomyocytes with catalase or NAC. Cells transiently transfected with the dominant positive mutant of p21ras (RasL61) led to a significant increase in intracellular ROS. Concomitantly, the mRNA levels and the promoter activities of c-fos were also induced. In contrast, cells transfected with the dominant negative mutant of Ras (RasN17) inhibited Et-1-induced ROS. Consistently, the increase of c-fos mRNA levels and promoter activities by Et-1 were also inhibited. CONCLUSIONS: These findings clearly indicate that Et-1 treatment to cardiomyocytes can induce ROS via Ras pathway and the increased ROS are involved in the increase of c-fos expression. Our studies thus emphasize the importance of ROS as second messengers in Et-1-induced responses on cardiomyocytes.

Animals↗

PubMed1999

Age-related differences in corticosterone secretion in female rats.

The effects of age on steroidogenesis in rat zona fasciculata-reticularis (ZFR) cells were studied. Young, adult, and middle-aged rats were ovariectomized (Ovx) and received replacement therapy with oil or estradiol benzoate ([EB] 25 microg/mL/kg). Rat ZFR cells were incubated with corticotropin (ACTH), prolactin (PRL), or forskolin at 37 degrees C for 1 hour. The effects of age on the activity of steroidogenic enzymes of ZFR cells were measured by the amount of intermediate steroidal products separated by thin-layer chromatography. Plasma levels were higher for PRL (54% to 254%) and corticosterone (179% to 257%) in middle-aged versus young rats. In oil-treated Ovx rats, basal and ACTH-stimulated corticosterone release by ZFR cells were also greater in middle-aged compared with young rats. Replacement with EB in Ovx rats increased the ACTH-stimulated release of corticosterone. Administration of ovine PRL in vitro resulted in a dose-dependent increase of corticosterone production. In oil-treated middle-aged rats, ovine PRL-stimulated corticosterone release was higher than in young rats. Forskolin-induced production of cyclic adenosine 3',5'-monophosphate (cAMP) was greater in middle-aged versus young rats and correlated with the increase of corticosterone production. The activity of steroidogenic enzymes in rat ZFR cells was unchanged by age. These results suggest that the age-related increase of corticosterone production in female rats is associated with the stimulatory effect of PRL on ZFR cells and is due in part to an increase of cAMP generation.

3-Hydroxysteroid Dehydrogenases↗