In the monkey dorsal raphe, we reported that 1-month (mo) of estrogen replacement, with or without progesterone supplementation for 14 days, significantly increased tryptophan hydroxylase-1 (TPH-1) mRNA; decreased serotonin reuptake transporter (SERT) mRNA and decreased monoamine oxidase (MAO)-A mRNA, but had no effect on MAO-B mRNA. Here, we questioned what effect would 1 or 5 mo of ovarian hormones or the selective estrogen receptor modulator (SERM), raloxifene, have on TPH protein and phosphorylation, and on protein expression of SERT, MAO-A or MAO-B? Raloxifene antagonizes estrogen in breast or uterus, but estrogen-like activities in the brain have been reported. Cytoplasmic and membrane extracts of the dorsal raphe region were processed for Western blotting. TPH, phosphoserine, SERT, MAO-A, and MAO-B were detected with specific antibodies. The optical densities of the signals were measured with NIH image and analyzed by ANOVA. Both 1 and 5 mo of estrogen, with or without progesterone, and 5 mo of raloxifene significantly increased TPH protein. Administration for 5 mo of estrogen plus progesterone and raloxifene also increased TPH phosphorylation. Estrogen, with or without progesterone, for 1 mo had no effect on SERT protein. However, 5 mo of estrogen and 5 mo of raloxifene increased SERT protein. Estrogen alone or combined with progesterone for 1 mo caused a significant reduction in MAO-A. Yet, after 5 mo of the same treatments, MAO-A was not different from spayed controls. Estrogen alone had no effect on MAO-B. However, the addition of progesterone significantly increased MAO-B. Raloxifene for 5 mo had no effect on MAO-A or MAO-B. Thus, to various extents, estrogen, progesterone, and raloxifene may increase serotonin production and transport. The expression of the degradative enzymes suggests a complex combination of gene transcription, post-transcriptional processing, and substrate feedback mechanisms.

The results clearly indicate that laboratory-determined enzyme concentrations in feeding tube aspirates are helpful in predicting tube location. Thus, it is desirable that inexpensive, simple bedside tests be developed so that they can be used in conjunction with pH measurements to help predict tube position.

Preliminary laboratory-based data indicate that appropriate use of the proposed algorithm could significantly reduce the number of x-rays needed to exclude respiratory placement and to distinguish between gastric and intestinal placement.