Volunteers with systemic lupus erythematosus were recruited for a telephone service to provide psychosocial support to peers. The volunteers attended an 8-week counselor training program. The aim was to evaluate the impact of the training on counselors' skill development and to record possible changes in the counselors' psychosocial status. A second group of trainees (n = 15) was used as a delayed control for the first group (n = 14). The data were analyzed using multivariate repeated measures analysis of variance. Tests chosen to monitor psychosocial status included: Arthritis Impact Measurement Scales Anxiety and Depression subscales, Arthritis Helplessness Index, Wallston General Self-Efficacy Scale, University of California at Los Angeles Loneliness Scale, Rosenberg Self-Esteem, and Campbell Personal Competence scales. Tests selected to measure skills and knowledge.

Clinical Competence↗

PubMed1993

Effects of transforming growth factor beta and epidermal growth factor on steroid 5 alpha-reductase activity in genital skin fibroblasts.

Regulation of steroid 5 alpha-reductase (5 alpha R) activity and dihydrotestosterone (DHT) formation is central to prostate and sexual skin (hair) growth and cell function. Transforming growth factor-beta 1 (TGF-beta 1) is a ubiquitous peptide present in skin and scrotal tissue and its receptor is universally expressed. We have explored the role of TGF-beta 1 and -beta 2 on androgen formation in skin. Rat or human sexual skin fibroblasts were grown in primary cultures (passage 3-7). 5 alpha-Reductase activity was measured by the %-conversion of tracer 3H-testosterone to dihydrotestosterone over a 4 h period. Incubation of scrotal fibroblasts (2 x 10(5) cells) in serum and growth factor free media with androgen, such as DHT for two days significantly stimulates 5 alpha R in these cells (1.6-fold, p < 0.05 vs control). TGF-beta 1 alone at picomolar concentrations (2 x 10(-11) M to 2 x 10(-10) M) was a potent inducer of 5 alpha R activity in both rat (1.8-fold and 2.8-fold, respectively, p < 0.001 vs control at both doses) and human cells (TGF-beta 1 2 x 10(-10) M 3.3-fold, p < 0.001 vs control). Combined exposure of these fibroblasts to TGF-beta 1 (2 x 10(-10) M) and androgen (10(-7) M) further potentiated 5 alpha R activity (rat cells 6.5-fold, human cells 6.4-fold, p < 0.001 vs DHT or TGF-beta 1 alone).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed1993

Paracrine regulation of the renin-aldosterone system.

A number of clinical states have been described where there are derangements or discrepancies between renin-angiotensin and aldosterone secretion. We have studied the potential effect of some cytokines or growth factors (peptide regulatory factors) on this system in vitro. Both tumor necrosis factor/cachectin and interleukin I are potent regulators acting as renin secretagogues and inhibitors of aldosterone synthesis. These actions are mediated by prostaglandin cyclooxygenase products and their actions mimic the syndrome of hyperreninemic hypoaldosteronism in critical illness. Insulin and insulin-like growth factor I are also renin secretagogues in vitro However in a diabetic model (streptozotocin rat), there is resistance to both agonists as well as enhanced feedback suppression to angiotensin. A third peptide, transforming growth factor (TGF beta) has even more complex actions, acting as a secretagogue at low doses (10(-12) M) but inhibiting renin at higher doses. TGF beta production is increased in the diabetic state so that this peptide as well as the insulin family may be involved in hyporeninemic hypoaldosteronism.

Animals↗

PubMed1993

Transforming growth factor-beta is a renin secretagogue at picomolar concentrations.

Transforming growth factor-beta s (TGF-beta s), a family of peptides, have many actions including modulating cellular growth, differentiation, and influencing steroidogenesis. Because both TGF-beta and renin are present in renal juxtaglomerular cells, we have examined the effects of these peptides on renin secretion using static incubations of rat renal cortical slices. We report here an effect of both TGF-beta 1 and -beta 2 on renin secretion. At low concentrations, both TGF-beta 1 (4 x 10(-12) M) and -beta 2 (8 x 10(-12) M) stimulate basal renin secretion (control, 100 +/- 4%; TGF-beta 1, 123 +/- 4%; TGF-beta 2, 124 +/- 5%; both P < 0.02 compared with control). However, at higher concentrations (2 x 10(-10) M), both peptides do not alter basal renin release. Our previous studies show that both prostaglandins and lipoxygenase (LO) products of arachidonic acid play an important dual regulatory role in renin secretion; therefore, we have examined the effects of both cyclooxygenase (CO) and LO inhibition in TGF-beta action.(ABSTRACT TRUNCATED AT 250 WORDS)

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

PubMed1993

Androgen induction of steroid 5 alpha-reductase may be mediated via insulin-like growth factor-I.

The action of added insulin-like growth factor-I (IGF-I) and dihydrotestosterone (DHT) on steroid 5 alpha-reductase (5 alpha R) activity was studied using primary cultures of rat or human scrotal skin fibroblasts. Agents were added to cultured cells (2 x 10(5) cells) for 2 days, and enzyme activity was measured by the percent conversion of [3H] testosterone to DHT over a 4-h period in the absence of fetal calf serum or other growth factors. DHT, but not testosterone, at 10(-7) M significantly increased 5 alpha R activity (rat, 1.5 +/- 0.3% to 3.0 +/- 0.4%; human, 7.6 +/- 1.7% to 11.4 +/- 2.9%; P < 0.01). IGF-I (10(-9)-6.4 x 10(-9) M), but not IGF-II (10(-9)-10(-8) M) or insulin (10(-9)-10(-7) M), increased enzyme activity in a dose-related fashion [i.e. 1.5 +/- 0.5 to 10 +/- 2 in rat and 6.0 +/- 1.1 to 9.8 +/- 1.6% (P < 0.01) in human cells]. No change in cell numbers was observed in any experiment. Since the effect of IGF-I was about 100 times that of androgen, we studied the possibility that androgen induction of the enzyme activity could be via IGF-I production. Addition of a monoclonal antibody against IGF-I significantly reduced the effect of DHT, and simultaneous addition of a specific IGF-I receptor antibody blocked the expected induction of 5 alpha R activity (control, 4.9 +/- 0.5; DHT, 8.0 +/- 1.9; DHT plus IGF-I receptor antibody, 3.7 +/- 0.4%). No effect on 3 alpha-reduction of [3H]DHT to 3 alpha-androstanediol was detected in separate experiments. These studies indicate that IGF-I may be an important regulator of skin 5 alpha R activity and, thus, may influence DHT formation. The previously known androgen induction of this peripheral steroidogenic enzyme may be via paracrine/autocrine production of an IGF-I-type growth factor.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗