Bernard I. Grosser

Behavioral and electrophysiological effects of androstadienone, a human pheromone

Androstadienone is the most prominent androstene present on male human axillary hair and on the male axillary skin surface. We have previously shown that this volatile steroid is able to stimulate [corrected] the human female vomeronasal organ in picogram (pg) quantities, resulting in changes in autonomic activity. These effects are gender-specific. The purpose of the present study was to ascertain whether androstadienone could be considered a human pheromone by altering behavior as well as autonomic function. Forty normal female subjects were randomized in a double-blind manner to receive either control or 100 pg of androstadienone directly to the vomeronasal organ. We report that administration of this steroid under these conditions results in a significant reduction of nervousness, tension and other negative feeling states. Concordant changes were observed in autonomic physiology.

Effect of putative pheromones on the electrical activity of the human vomeronasal organ and olfactory epithelium

The summated receptor potential was recorded from the vomeronasal organ (VNO) and olfactory epithelium (OE) of 49 human subjects of both sexes (18 to 55 years old) using surface non-polarizable silver-silver chloride electrodes. 15-25 pg of human putative pheromones, clove oil and a diluent were administered to the VNO or the OE in 0.3-1 s pulses from a 0.05 mm dia cannula connected to a multichannel delivery system. Local stimulation of the VNO produces negative potentials of 1.8-11.6 mV showing adaptation. Responses are not obtained when the recording electrode is placed in the nasal respiratory mucosa. Pheromone ER-830 significantly stimulates the male VNO (P less than 0.01; n = 20), while ER-670 produces a significant effect on female subjects (P less than 0.001; n = 20). The other pheromones tested do not show significantly different effects in both male and female (P greater than 0.1). Similar quantities of odorant or diluent produce an insignificant effect on the VNO. Stimulation of the OE with clove oil produces depolarization of 12.3 +/- 3.9 mV, while pheromones do not show a significant effect. Our results show that the VNO is a functional organ in adult humans having receptor sites for human putative pheromones.

Ultrastructure of the human vomeronasal organ.

Virtually all vertebrates have a vomeronasal system whose involvement in pheromone detection plays a crucial role in reproduction. In humans, the vomeronasal organ has been assumed to be vestigial or absent and without functional significance. In the present study involving over 400 subjects, vomeronasal pits were observed in all individuals except those with pathological conditions affecting the septum. Electron microscopy of the adult human vomeronasal organ indicates the presence of two potential receptor elements in the pseudostratified epithelial lining: microvillar cells, and unmyelinated, intraepithelial axons. In addition, unmyelinated axons are common in the lamina propria surrounding the organ. They appear to constitute the components essential for a functional chemosensory system, and may thus provide the basis for a pheromone detection system as in other animals.

Fluoxetine, a selective serotonin uptake inhibitor, for the treatment of outpatients with major depression.

In a double-blind, placebo-controlled study the authors found that fluoxetine, a potent and selective inhibitor of serotonin reuptake, was an effective antidepressant in moderately depressed, ambulatory outpatients. Typical adverse effects reported by patients treated with fluoxetine included agitation, nausea, fatigue, and insomnia. Compared to imipramine, fluoxetine was associated with fewer complaints of dry mouth, constipation, and dizziness.

Properties of corticosterone-binding macromolecules from rat brain cytosol

Abstract A partial characterization has been made of [ 3 H]corticosterone-binding macromolecules from the cytosols of rat brain. The macromolecules are protein(s) and appear to have a molecular weight in excess of 200,000 because of migration characteristics on Sephadex and Sepharose 4B. Binding properties were measured which showed that the K dissoc is 2.7 × 10 −10 and 0.47 pmoles of corticosterone are bound/mg of protein, indicating a high affinity and limited capacity for [ 3 H]corticosterone. Competitive binding studies were performed which indicate that the protein(s) have a high degree of specificity for [ 3 H]corticosterone including stereospecificity. Based on its biological potency, dexamethasone did not compete with corticosterone for binding sites to the extent expected. Examination of rat brains with respect to their capacity to bind [ 3 H]corticosterone in vitro indicated that the greatest concentration of cytosol-binding molecules was localized in the hippocampus. Evidence was obtained that the corticosterone-binding protein in brain cytosol is not corticosteroid-binding globulin (CBG).

Decreased beta-adrenergic receptors in rat brain after chronic administration of the selective serotonin uptake inhibitor fluoxetine

Fluoxetine, a novel antidepressant compound that potently and selectively inhibits serotonin uptake, was chronically administered to laboratory rats. Using in vitro receptor autoradiographic techniques, we found that the binding of [3H]-dihydroalprenolol ([3H]-DHA) decreased significantly in frontal cortex layers. Analysis of saturation experiments indicated that the reduction was due to a change in number but not affinity of [3H-DHA binding sites. The data support the hypothesis that the mechanism of action of most antidepressant compounds involves a change in beta-adrenergic receptor function.

The ontogeny of corticosterone and dexamethasone receptors in rat brain

Abstract The ontogeny of [ 3 Hcorticosterone and [ 3 Hdexamethasone receptor macromolecules in cytosol derived from brains of adrenalectomized rats 2–30 days of age was studied. The binding of [ 3 Hcorticosterone in male rats perfused at sacrifice with ice-cold isotonic sucrose in buffer, 2–8 days of age, ranged from 100 to 133 fmoles/mg protein. Binding increased from 133 to 356 fmoles/mg protein between 8 and 19 days of age, then decreased slightly between 19 and 30 days of age. [ 3 HDexamethasone binding under similar conditions was comparable to that of corticosterone from 3 to 8 days of age, but in older animals the amount of receptor-bound [ 3 Hdexamethasone was two-thirds that of corticosterone. Binding of these steroids in female rats was similar to that in male rats. The apparent dissociation constants for [ 3 Hcorticosterone and [ 3 Hdexamethasone were equal, and they did not change with age. In all age groups studied, unlabeled corticosterone competed more strongly for [ 3 Hcorticosterone binding sites than did unlabeled dexamethasone, but both steroids competed equally well for [ 3 Hdexamethasone binding sites. Although qualitatively similar at all ages, competition by unlabeled corticosterone and dexamethasone binding sites showed quantitative differences as the animal matured. For example, there was less competition for binding sites in 5-day-old animals than in older animals. These results indicate that binding sites for [ 3 Hcorticosterone and [ 3 Hdexamethasone in neonatal brain may be less specific than in the more mature brain. Also, the increase in the number of binding sites with age can be correlated with known physiological changes in the developing pituitary-adrenal axis.

5-Hydroxytryptophan: a review of its antidepressant efficacy and adverse effects

Alterations in serotonin metabolism may be an important factor in the etiology and treatment of depression. In this regard, 5-hydroxytryptophan (5-HTP), a serotonin precursor, has been given to patients with depression. Although a review of these studies suggests that 5-HTP possesses antidepressant properties, additional trials are clearly indicated. Following a discussion of the pharmacology of 5-HTP, the authors highlight adverse effects associated with its administration to depressed patients, neurologic subjects, and normal individuals. Relatively few adverse effects are associated with its use in the treatment of depressed patients.

Corticosterone binding by rat brain cytosol.

Significant quantities of corticosterone were associated with macromolecules of the brain cytosol following intrathecal administration of [3H]corticosterone to adrenalectomized rats. Fifteen times more steroid was found associated with proteins from adrenalectomized rats than from control animals or adrenalectomized animals pretreated with corticosterone. Pretreatment of adrenalectomized rats with 11‐dehydrocorticosterone, Cortisol and cortisone decreased the amount of [3H]corticosterone found associated with protein, whereas progesterone, oestradiol and testosterone did not interfere with the association of [3H]corticosterone with macromolecules of the cytosol. Further evidence for protein‐steroid interaction was obtained by incubating [3H]corticosterone (B), [3H]cortisol (F), or 11‐[3H]deoxycortisol (S) with brain cytosols. The degree of binding was in the order B > F > S.

Effect of steroid competition and time on the uptake of [3H]corticosterone in the rat brain; An autoradiographic study

The localization of [3H]corticosterone in the brain and pituitary of the adrenalectomized rat was studied by autoradiography. Corticosterone was concentrated preferentially by neurons in the hippocampus, septum, amygdala, and neocortex, with the hippocampal and septal neurons having the greatest concentration. [3H]-Corticosterone localization was significantly greater in neurons from adrenalectomized animals. Administration of unlabeled corticosterone (3 mg) 30 min before injection with [3H]corticosterone significantly decreased cellular localization of the labeled corticosterone, whereas [3H]corticosterone localization was not affected by progesterone pretreatment. Animals were sacrificed 15, 30 and 120 min after the injection of [3H]corticosterone to study the distribution of the hormone over the cytoplasm and nuclei. Silver grains were localized primarily over the cytoplasm of the concentrating neurons 15 min after injection; however, by 30 min after injection they were evenly distributed over both nuclei and cytoplasm.