TY - JOUR
T1 - Ovarian steroid action on tryptophan hydroxylase protein and serotonin compared to localization of ovarian steroid receptors in midbrain of guinea pigs
AU - Lu, N. Z.
AU - Shlaes, T. A.
AU - Gundlah, C.
AU - Dziennis, S. E.
AU - Lyle, R. E.
AU - Bethea, Cynthia L.
N1 - Funding Information:
We thank Dr. David Hess, Director of the Hormone Assay Core of the P30 Population Center grant for assistance with the steroid hormone assays. This work was supported by NIH grant HD17269, P30 Population Center Grant HD18185, and RR00163 for operation of the Oregon Regional Primate Research Center.
PY - 1999
Y1 - 1999
N2 - The effect of estrogen (E) and progesterone (P) on the protein expression of the rate-limiting enzyme in serotonin synthesis, tryptophan hydroxylase (TPH), and the level of serotonin in the hypothalamic terminal field was examined in guinea pigs. In addition, we questioned whether serotonin neurons of guinea pigs contain ovarian steroid receptors (estrogen receptor-α[ERα], estrogen receptor β[ERβ], progestin receptors [PRs]) that could directly mediate the actions of E or P. Western blot and densitometric analysis for TPH were used on raphe extracts from untreated- ovariectomized (OVX), OVX-E-treated (28 d), and OVX-E+P-treated (14 d E+14 d E+P) guinea pigs. The medial basal hypothalami from the same animals were extracted and subjected to high-performance liquid chromatography analysis for serotonin, dopamine, 5-hydroxyindole acetic acid, and homovanillic acid. The brains from other animals treated in an identical manner were perfusion fixed and examined for the colocalization of ERα plus serotonin and PR plus serotonin with double immunohistochemistry or for expression of ERβ mRNA with in situ hybridization. E and E+P treatment significantly increased TPH protein levels compared to the untreated control group (p < 0.05), but TPH levels were similar in the E and E+P-treated groups. By contrast, serotonin (nanogram/milligram of protein) in the hypothalamus was significantly increased by E+P treatment, but not by E alone. Neither ERα nor PR proteins were detected within serotonin neurons of the guinea pig raphe nucleus. However, ERβ mRNA was expressed in the dorsal raphe. In summary, E alone increased TPH protein expression and the addition of P had no further effect, whereas E+P increased hypothalamic serotonin and E alone had no effect. The localization of ERβ, but not ERα or PR, in the dorsal raphe nucleus suggests that E acting via ERβ within serotonin neurons increases expression of TPH, but that P acting via other neurons and transsynaptic stimulation may effect changes in TPH enzymatic activity, which in turn, would lead to an increase in serotonin synthesis.
AB - The effect of estrogen (E) and progesterone (P) on the protein expression of the rate-limiting enzyme in serotonin synthesis, tryptophan hydroxylase (TPH), and the level of serotonin in the hypothalamic terminal field was examined in guinea pigs. In addition, we questioned whether serotonin neurons of guinea pigs contain ovarian steroid receptors (estrogen receptor-α[ERα], estrogen receptor β[ERβ], progestin receptors [PRs]) that could directly mediate the actions of E or P. Western blot and densitometric analysis for TPH were used on raphe extracts from untreated- ovariectomized (OVX), OVX-E-treated (28 d), and OVX-E+P-treated (14 d E+14 d E+P) guinea pigs. The medial basal hypothalami from the same animals were extracted and subjected to high-performance liquid chromatography analysis for serotonin, dopamine, 5-hydroxyindole acetic acid, and homovanillic acid. The brains from other animals treated in an identical manner were perfusion fixed and examined for the colocalization of ERα plus serotonin and PR plus serotonin with double immunohistochemistry or for expression of ERβ mRNA with in situ hybridization. E and E+P treatment significantly increased TPH protein levels compared to the untreated control group (p < 0.05), but TPH levels were similar in the E and E+P-treated groups. By contrast, serotonin (nanogram/milligram of protein) in the hypothalamus was significantly increased by E+P treatment, but not by E alone. Neither ERα nor PR proteins were detected within serotonin neurons of the guinea pig raphe nucleus. However, ERβ mRNA was expressed in the dorsal raphe. In summary, E alone increased TPH protein expression and the addition of P had no further effect, whereas E+P increased hypothalamic serotonin and E alone had no effect. The localization of ERβ, but not ERα or PR, in the dorsal raphe nucleus suggests that E acting via ERβ within serotonin neurons increases expression of TPH, but that P acting via other neurons and transsynaptic stimulation may effect changes in TPH enzymatic activity, which in turn, would lead to an increase in serotonin synthesis.
KW - Estrogen receptor- β
KW - Estrogen receptor-α
KW - Progestin receptor
KW - Serotonin
KW - Tryptophan hydroxylase
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U2 - 10.1385/endo:11:3:257
DO - 10.1385/endo:11:3:257
M3 - Article
C2 - 10786822
AN - SCOPUS:0033510004
SN - 1355-008X
VL - 11
SP - 257
EP - 267
JO - Endocrine
JF - Endocrine
IS - 3
ER -