Expression of proopiomelanocortin and proenkephalin mRNA in sexually dimorphic brain regions are altered in adult male and female rats treated prenatally with morphine.
ABSTRACT The present study demonstrates that prenatal morphine exposure on gestation days 11-18 differentially alters proopiomelanocortin (POMC) and proenkephalin (pENK) mRNA in the hypothalamus and limbic system of adult male and female rats. In adult, prenatally morphine-exposed male rats POMC mRNA levels are decreased in the arcuate nucleus of the hypothalamus (ARC), while the pENK mRNA levels are increased in the paraventricular nucleus of the hypothalamus (PVN) and in the ventrolateral subdivision of the ventromedial nucleus of the hypothalamus (VMH), specifically in the ventrolateral subdivision of the VMH. In adult, prenatally morphine-exposed female rats, POMC mRNA levels in the ARC are increased in ovariectomized (OVX) but not in OVX, estradiol benzoate- (EB) or EB- and progesterone- (P) treated females. In contrast, pENK mRNA levels are decreased in the VMH of morphine-exposed, OVX females and increased in EB-treated females. Further, prenatal morphine exposure decreases pENK mRNA in the ARC and increases it in the medial pre-optic area independently of female gonadal hormones. Finally, POMC mRNA levels are increased in the ARC of saline-exposed, EB- or EB- and P-treated females but not in OVX females. Thus, the present study suggests that prenatal morphine exposure sex and brain region specifically alters the level of POMC and pENK mRNA.
- Progress in brain research 02/1978; 48:291-308. · 4.19 Impact Factor
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ABSTRACT: The display of lordosis behavior has been correlated with the estrogen-induced expression of cholecystokinin (CCK) and enkephalin within the limbic-hypothalamic circuit. These neuropeptides have opposing effects on lordosis; for example, in the medial preoptic nucleus, CCK facilitates and opiates inhibit lordosis. Antisense oligodeoxynucleotide blockade of receptor expression indicated that CCK modulates lordosis in the medial preoptic nucleus through the CCK(A)-receptor. Sequence-specific antibodies directed against delta- and mu-opiate receptor proteins labeled fibers in the medial preoptic nucleus. Estrogen treatment of ovariectomized rats or etorphine (a nonselective opiate agonist) treatment altered the appearance of the immunoreactivity from a diffuse pattern to one of distinctly stained mu-opiate receptor immunoreactive cells and varicose fibers in the medial preoptic nucleus. Such a pattern of staining reflects an internalization of mu-opiate receptors following agonist stimulation. This type of internalization has been used as an indication of synaptic activity. The distribution of receptor internalization surrounds the distribution of CCK cells in the medial preoptic nucleus, suggesting that endogenous opioid peptides may modulate estrogen-induced CCK mRNA expression. Interestingly, nonselective and delta-opiate receptor selective antagonists potentiated the estrogen-induced CCK mRNA expression in the medial preoptic nucleus. Together, these results suggest that endogenous opioid peptides may modulate the estrogenic upregulation of CCK mRNA expression and demonstrate an important level of regulation of gene expression in which synaptic activity modifies hormonal input.Brain Research Bulletin 02/1997; 44(4):335-43. · 2.94 Impact Factor
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ABSTRACT: Hormone effects on proenkephalin (PE) mRNA allow an opportunity to compare a brain region-specific molecular change with a quantifiable behavior. Slot blots were used to measure PE mRNA levels in the ventromedial hypothalamus (VMN) and preoptic area (POA) as a function of the dose of estrogen administered to ovariectomized rats. Every rat used had been characterized for the ability to display lordosis behavior. Estradiol treatment led to a monotonic dose-dependent increase in PE mRNA level in VMN, while only a small effect was observed in POA at the higher estradiol doses. Lordosis behavior, assessed manually and in mating tests, also increased monotonically with estradiol dose. The data indicate that an apparent 'threshold' level of PE mRNA in VMN coincided wit display of behavior, and suggest further that high levels of PE mRNA, alone, are not sufficient for lordosis. While the exact relationship of the eventual product, Met-enkephalin, to female reproductive behavior remains to be determined, the parallel changes in PE mRNA level and behavior encourage further analysis.Molecular Brain Research 07/1990; 8(1):47-54. · 2.00 Impact Factor