Rapid and opposite effects of cortisol and estradiol on human erythrocyte Na+,K+-ATPase activity: relationship to steroid intercalation into the cell membrane.

We determined whether two naturally occurring steroids, cortisol and 17beta-estradiol (E2), can rapidly modulate the activity of an important membrane protein, human erythrocyte (RBC) Na+,K+-ATPase, an enzyme that does not bind either hormone directly. We also determined the membrane binding locations for cortisol and E2 and their effects on membrane molecular structure and fluidity. Direct application of both steroids to intact human RBC significantly altered maximum ouabain-sensitive 86Rb uptake within 5 min: Cortisol decreased it by 24%, whereas E2 increased it by 18%. As determined by small angle x-ray diffraction, these steroids occupied distinct time-averaged binding locations in the RBC membrane, cortisol localizing near the bilayer surface, 14-29 A from the bilayer center, and E2 localizing deep within the hydrocarbon core, 0-7 A from the bilayer center. Neither steroid significantly changed overall bilayer width or membrane fluidity. These data suggest that cell membrane protein function can be altered rapidly and differentially by naturally occurring steroids. This effect did not appear to be related to the different binding locations of the steroids in the membrane or to their influence on membrane fluidity.

Biophysical membrane interactions of steroid hormones: a potential complementary mechanism of steroid action.

There is strong evidence to support the hypothesis that the rapid effects of steroids on neurons are membrane-mediated. Rapid steroid effects have been demonstrated in the absence of intracellular receptors, in the presence of RNA or protein synthesis inhibitors, and in response to steroids coupled to large proteins that block access to intracellular receptors. This study selectively reviewed the emerging body of evidence suggesting that steroids have multiple sites of cellular actions, and explored in depth one possible membrane-mediated mechanism of action, the membrane-intercalation model.

Steroid hormones partition to distinct sites in a model membrane bilayer: direct demonstration by small-angle X-ray diffraction.

The classical, genomic mechanisms of steroid hormone action cannot account for their rapid cellular effects. Membrane-bound steroid receptors have been partially characterized, but many rapid steroid effects occur in the absence of steroid-protein binding. Although it has been proposed that these effects could be due to steroid-induced biophysical alterations of the cell membrane, only indirect supporting evidence for this hypothesis has been forthcoming. In the present study, the ability of cortisol and estradiol (E2), natural steroids of different lipophilicity, to induce alterations in a model membrane (lecithin) bilayer was examined directly by small-angle X-ray diffraction under physiologic-like conditions. Within minutes, both steroids partitioned to distinct sites in the membrane. With increasing membrane cholesterol content, cortisol was displaced toward the polar headgroup region of the phospholipid bilayer, whereas E2 was displaced in the opposite direction, toward the nonpolar hydrocarbon core. Membrane-based partition coefficients (Kp[mem]) for both steroids (>100:1) were highest at those cholesterol concentrations that displaced the steroids toward the headgroup region (high cholesterol for cortisol; low for E2). Both steroids, when located in the headgroup region, increased overall bilayer width by 3-4 A, a change that could modulate the structure and function of integral membrane proteins independent from steroid effects on the genome.

Impact of psychotherapy. Does it affect frequency of visits to family physicians?

OBJECTIVE: To investigate whether a course of psychotherapy with a psychologist affected the frequency of patients' visits to their family doctors. DESIGN: Retrospective analysis of patients' medical records to determine the frequency of visits to their family doctors in the 6 months before psychotherapy, during therapy, and in the 6 months after therapy. SETTING: A teaching family medical centre in London, Ont. PARTICIPANTS: Thirty-three patients who had completed a course of psychotherapy between 1984 and 1991. INTERVENTIONS: Psychotherapy was provided by two psychologists employed at the medical centre. Patients did not pay a direct fee. The median length of psychotherapy was 12.5 1-hour sessions, and the therapeutic approach was eclectic and humanistic. MAIN OUTCOME MEASURES: Frequency of visits to family physicians before, during, and after psychotherapy. RESULTS: Frequency of visits to family doctors decreased both during and after psychotherapy. The decrease was especially apparent from before therapy to after therapy (49%, P < .001). Psychotherapy given by psychologists in a Canadian family medical centre appears to follow the pattern of the "offset effect," a reduction in medical use following psychotherapy, which has been demonstrated in other medical settings. CONCLUSIONS: Psychotherapy can be an effective and efficient part of total medical care for patients with complex psychological problems.

Managing erotic feelings in the physician-patient relationship.

In spite of prohibitions against the sexual involvement of physicians with their patients, erotic feelings sometimes arise in physician-patient relationships. The authors suggest that physicians can protect themselves and their patients from the harm that results from sexual involvement by establishing behavioural limits for their professional relationships, responding to patients' sexual overtures in a firm but nonjudgemental manner, examining their own sexual feelings rationally, seeking consultation if necessary and terminating the relationship if sexual feelings are compromising patient care. The challenge for physicians is to acknowledge that sexual feelings can arise and to manage such feelings for the sake of their own and their patients' well-being.

Cholecystokinin (CCK)-induced stimulation of luteinizing hormone (LH) secretion in adult male rhesus monkeys: examination of the role of CCK in nutritional regulation of LH secretion.

Studies were performed with the overall goal of testing the hypothesis that cholecystokinin (CCK), a peptide hormone released from the gastrointestinal tract in response to meal consumption, provides a metabolic signal which modulates LH secretion in response to changes in the body's nutritional intake. In an initial study to document the effects of CCK on LH secretion in adult male rhesus monkeys, sulfated CCK-8 (7 and 15 micrograms/kg) was administered to six monkeys, and blood samples were collected from indwelling venous catheters. The 15-micrograms/kg dose of CCK elicited a rapid release of LH, with peak LH levels of 31.29 +/- 7.19 ng/ml occurring within 5-15 min. To determine the CCK receptor type mediating the effect of CCK on LH secretion, specific CCK type-A (L-364,718) and type-B (L-365,260) receptor antagonists (1 mg/kg) were administered to five monkeys 15 min before CCK administration. The CCK-A antagonist completely blocked LH secretion in response to CCK, whereas the CCK-B antagonist had no effect. To assess whether endogenous CCK, released in response to food intake, stimulates LH secretion, six monkeys were fasted for 1 day and then provided with a normal meal of monkey chow (i.e. a refeed meal) the following day, with either no antagonist, CCK-A antagonist, or CCK-B antagonist administered 30 min before the meal. As previously demonstrated, meal consumption after a brief period of fasting caused a rapid stimulation of pulsatile LH secretion. The refeed meal led to a comparable stimulation of LH secretion regardless of whether monkeys received no antagonist (3.7 +/- 0.44 LH pulses/9 h), CCK-A antagonist (3.33 +/- 0.56 LH pulses/9 h), or CCK-B antagonist (4.0 +/- 0.78 LH pulses/9 h). These results indicate that CCK can stimulate LH secretion in adult male rhesus monkeys, acting via type-A CCK receptors. However, endogenous CCK released in response to meal intake does not appear to be responsible for the meal-induced stimulation of LH secretion that occurs when monkeys are fed a normal meal after a brief period of fasting.

A "magic" aid for hypnosis and suggestion in crisis management: a brief communication.

Within the context of crisis management, in certain cases the transfer of a small object from therapist to patient has had positive outcomes. Examples of the use of this "magic" aid are provided with some background and a tentative rationale. Caution regarding its use is suggested.