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Biotech / Medical : Ligand (LGND) Breakout! -- Ignore unavailable to you. Want to Upgrade?

To: buyhiman who wrote (16566)	3/5/1998 4:42:00 PM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

Carl, There have been many correlative studies that show benefits of estrogen in preventing Alzheimer or improving memory. A recent report found a correlation with the size (small) of the cholea and a tendency of females to be gay. The size is determined in utero by hormones (androgens). Thus it seems highly likely that hormones can have an influence. LGND apparently plans on using designer estrogens to get the benefits of estrogen (delaying or preventing Alzheimers and improving memory), without the side effects (stimulate uterine tissue in females and feminizing effects in males). LGND has extensive programs in that area (PFE's Droloxifene and CP-366,156 are in the clinic while AHP's TSE424 is slated to enter the clinic this month). Moreover, LGND has a research program with LLY to investigate the enhancing effect that rexinoids (Targretin) have on designer estrogens (Evista). Thus, any of the above designer estrogens may have a positive effect on the CNS, and such an effect could be potentiated by rexinoids. Vilar headed up AHP's Premarin program, so I'm sure that he is interested. Since Premarin is a $1 Billion drug, I'm sure that AHP is interested also.

To: buyhiman who wrote (16566)	3/5/1998 4:53:00 PM
From: Henry Niman	Read Replies (2) \| Respond to of 32384

Carl, The effect of hormones on bird brains may be of interest to some of the posters on this board: J Neurobiol 1988 Oct;19(7):624-635 Joint hormonal and sensory stimulation modulate neuronal number in adult canary brains. Bottjer SW, Dignan TP Department of Biology, University of Southern California, Los Angeles 90089-0371. Treatment of adult female canaries with testosterone (T) causes them to produce male-typical vocalizations and results in striking growth of brain nuclei that control song behavior (Nottebohm, 1980). The song-control nucleus HVc (caudal nucleus of the ventral hyperstriatum) contains cells that concentrate testosterone or its metabolites, suggesting that steroid hormones may induce the growth of HVc directly by regulating the expression of specific genes in those HVc neurons that have steroid receptors. However, we have previously provided evidence that is inconsistent with the idea that steroids promote growth of HVc solely via a direct action on hormone receptors: testosterone treatment of deafened adult females results in very little growth of HVc, relative to T-treated hearing birds (Bottjer et al., 1986b). Thus, birds in the former group undergo very little overall growth of HVc despite high circulating levels of hormone. We show here that the slightly increased size of HVc in T-treated deaf birds is attributable to an increase in neuronal spacing; the greatly increased size of HVc in T-treated hearing birds is due to an increase in neuronal number as well as spacing. There was virtually no increase in number of HVc neurons in T-treated deafened birds relative to control groups, whereas T-treated hearing birds showed a marked increase in neuron number. The song-control nucleus RA (robust nucleus of the archistriatum), which receives direct afferent input from HVc, also increases in size in response to testosterone treatment. However, the volume of RA increases in both hearing and deafened birds; this increase is primarily due to an increase in neuronal spacing as well as a small increase in neuron number. These results demonstrate that the number of neurons in a specific vocal-control nucleus (HVc) can change dramatically in adult canaries and suggest that some synergistic action of hormonal and sensory stimulation is necessary to induce such a change. PMID: 3225559, UI: 89140739