Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 receptor.

Dopamine, through D2 receptor (D2R), is the major regulator of lactotrope function in the anterior pituitary gland. Both D2R isoforms, long (D2L) and short (D2S), are expressed in lactotropes. Although both isoforms can transduce dopamine signal, they differ in the mechanism that leads to cell response. The administration of D2R agonists, such as cabergoline, is the main pharmacological treatment for prolactinomas, but resistance to these drugs exists, which has been associated with alterations in D2R expression. We previously reported that dopamine and cabergoline induce apoptosis of lactotropes in primary culture in an estrogen-dependent manner. In this study we used an in vivo model to confirm the permissive action of estradiol in the apoptosis of anterior pituitary cells induced by D2R agonists. Administration of cabergoline to female rats induced apoptosis, measured by Annexin-V staining, in anterior pituitary gland from estradiol-treated rats but not from ovariectomized rats. To evaluate the participation of D2R isoforms in the apoptosis induced by dopamine we used lactotrope-derived PR1 cells stably transfected with expression vectors encoding D2L or D2S receptors. In the presence of estradiol, dopamine induced apoptosis, determined by ELISA and TUNEL assay, only in PR1-D2S cells. To study the role of p38 MAPK in apoptosis induced by D2R activation, anterior pituitary cells from primary culture or PR1-D2S were incubated with an inhibitor of the p38 MAPK pathway (SB203850). SB203580 blocked the apoptotic effect of D2R activation in lactotropes from primary cultures and PR1-D2S cells. Dopamine also induced p38 MAPK phosphorylation, determined by western blot, in PR1-D2S cells and estradiol enhanced this effect. These data suggest that, in the presence of estradiol, D2R agonists induce apoptosis of lactotropes by their interaction with D2S receptors and that p38 MAPK is involved in this process.

Comparative evaluation of the efficacy of four topical medications individually or in combination to treat grade I acne vulgaris.

A randomised study was carried out to evaluate the efficacy of four topical medications individually and in combination to treat grade I acne vulgaris which is characterised by mild lesions (< 10 in one side of face) consisting of predominantly comedones with occasional pustules in oily skin. Maintaining the inclusion and exclusion criteria 100 patients were selected and divided into 5 groups to receive different topical drugs at random basis in the dermatology OPD. Topical medication given to them is mentioned below against each group: Group I--retinonic acid, group II--benzoyl peroxide, group III--clindamycin, group IV--cleanser and group V--all the four medications. The patients were observed for reduction in number of comedones, suppression of papulopustules with healing rate, effects on facial skin, and rate of recurrence. Results were observed according to the groups. In group I old acne was reduced in size and gradually cleared off (80%). Recurrence was few with appearance of new microcomedones which were cleared off within short time. Skin became smoother and fresh. Texture became lighter in colour. In group II whiteheads were reduced at about 70% in number. Rate of recurrence was normal. Skin became rough and dry. In group III pustular acne healed better and faster. In group IV acne of oily skin healed better and faster. Rate of recurrence was normal. Skin became fresh and oil-free. In group V reduction of lesions was very much significant (90%) with quick healing rate of the comedones. Recurrence was normal but delayed. Skin became smoother, finer and fresher. So, combination therapy is better. Cleanser is always helpful even without medications.