We assessed whether fetal tissue containing the suprachiasmatic nuclei (SCN) can restore age-related changes in the diurnal rhythm of hypothalamic corticotropin-releasing hormone (CRH) and anterior pituitary proopiomelanocortin (POMC) mRNA. Young, middle-aged, and middle-aged SCN-transplanted rats were killed at seven times of day. In young rats, CRH mRNA exhibited a diurnal rhythm in the dorsomedial paraventricular nuclei but not in other subdivisions of the nuclei. No rhythm was detected in aging rats. SCN transplants restored a rhythm in CRH mRNA, but the timing was not precisely the same as in young animals. POMC mRNA exhibited a daily rhythm in young rats. Aging abolished the rhythm and decreased the average mRNA level; fetal transplants restored the rhythm, but the amplitude remained attenuated. These data are the first demonstration that fetal tissue can restore the diurnal rhythm of a neuroendocrine axis that is driven by the SCN. We conclude that the neuroendocrine substrate from the aging host remains capable of responding to diurnal cues to express diurnal rhythmicity in CRH/POMC mRNA when fetal SCN transplants confer the appropriate signals.
Estrogen is a robust stimulator of galanin synthesis and secretion in the anterior pituitary. Galanin is colocalized in lactotrophs in the estrogen-treated anterior pituitary, and its roles in lactotroph function are still being elucidated. In the present studies, we quantified the phenotypes of estrogen-treated Fischer 344 rat anterior pituitary cells expressing the galanin gene by dual in situ hybridization. The total population of galanin-positive pituitary cells increased from undetectable levels to 16% of all cells after 2 weeks of estrogen treatment. More than 90% of the galanin-positive cells coexpressed PRL messenger RNA, and one-third of the lactotrophs expressed galanin messenger RNA. We hypothesized that galanin in the anterior pituitary may contribute to the heterogeneous secretion of PRL, and that one of the functions of galanin is to regulate PRL secretion in an autocrine/paracrine manner. To test this hypothesis, we performed the reverse hemolytic plaque assay combined with in situ hybridization to measure PRL secretion and galanin gene expression within the same individual cells. PRL secretion from galanin-positive lactotrophs was significantly greater than that from galanin-negative lactotrophs. Moreover, treatment with galanin antiserum significantly attenuated PRL secretion from galanin-positive cells, and treatment with galanin significantly enhanced PRL secretion from galanin-negative lactotrophs. In conclusion, these data provide direct evidence that galanin derived from the estrogen-treated anterior pituitary stimulates PRL secretion in both autocrine and paracrine manners.
In young animals, the suprachiasmatic nuclei (SCN) of the hypothalamus, which are critical circadian pacemakers, exhibit a light-induced diurnal rhythm in Fos expression. The expression of this immediate-early gene has been used as an index of the activity of the SCN and their ability to respond to external cues that entrain them, such as light. In the present study, we show that by the time rats reach middle age baseline Fos expression increases prematurely during the dark and that light-induced Fos expression is blunted and delayed. We also demonstrate that transplantation of fetal tissue containing the SCN into the third cerebral ventricle of middle-aged rats enables aged hosts to regain the ability to exhibit diurnal patterns of Fos expression that are strikingly similar to those observed in young animals. Our findings lead to the following conclusions: 1) the diurnal pattern of activity of SCN cells is blunted in middle-aged rats, and 2) SCN transplants provide unique signals that enable the cellular systems of the host to regain rhythmic functional capabilities. These results provide new insights into the critical active role that the host plays in restoration of function evoked by the presence of a transplant.
The recently cloned leptin receptor (OB-R) is expressed in many tissues, including the anterior pituitary. It is not known whether OB-R gene expression is regulated by pituitary hormones. In the present study, we detected the long isoform of OB-R (OB-R(L)) in the anterior pituitary of normal mice using RT-PCR, but were unable to detect the short isoform (OB-R(S)). In human growth hormone-releasing hormone (hGHRH) transgenic mice, we discovered a significant increase in OB-R(L) mRNA levels in the anterior pituitary as compared to controls, and OB-R(S) gene expression was detectable. In contrast to the pituitary, there were no significant changes in OB-R gene expression for either isoform in the hypothalamus of hGHRH mice. The dramatic increase in the gene expression of OB-R(L) in the anterior pituitary of hGHRH transgenic mice was confirmed by RNase protection assay. This is the first study to demonstrate that OB-R gene expression in the anterior pituitary gland is increased by GH and/or GHRH.
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