Characterization of the inhibitory effects of hyperprolactinaemia on the mechanism controlling LH secretion in chronically ovariectomized rats

This study was designed to examine whether cyclosporine (CyA) acts on the endocrine system by modifying the pulsatile secretion pattern of prolactin and LH. Both pituitary-grafted and sham-operated rats were submitted to a subcutaneous vehicle or CyA (5 mg/kg) treatment daily for 10 days beginning on the day of surgery. Pituitary grafting and/or CyA administration changed the pulsatile pattern of prolactin observed in sham-operated animals. The mean values of serum prolactin were significantly increased by pituitary grafting and the treatment with CyA further increased them. The mean half-life of prolactin was significantly increased in pituitary-grafted rats and was not changed by CyA administration, although it was decreased in sham-operated rats. The frequency of prolactin pulses was significantly decreased in pituitary-grafted as compared to sham-operated controls and was not further modified by CyA administration. However, in sham-operated rats a significant decrease of this parameter was observed. Duration of the prolactin peaks was significantly increased by pituitary grafting, and was not modified by CyA administration in any of the groups studied. The absolute amplitude of the prolactin peaks was significantly increased in pituitary-grafted as compared to sham-operated animals, and the treatment with CyA further increased this parameter in both groups. Mean values of LH were significantly increased in pituitary-grafted as compared to control rats. CyA administration significantly increased LH levels in sham-operated rats and decreased them in pituitary-grafted animals. The mean half-life, the pulse frequency and the duration of LH peaks were not modified by either pituitary grafting or CyA administration. The absolute amplitude of LH peaks was significantly increased in pituitary-grafted animals as compared to the sham-operated group. Cy administration increased the absolute amplitude of LH peaks in sham-operated and reduced it in pituitary-grafted animals. The data suggest that CyA might act by modifying the pulsatile secretory patterns of prolactin and LH.

Section: Discussionsupporting

confidence: 84%

Cyclosporine Modifies the Pulsatile Secretory Patterns of Prolactin and Luteinizing Hormone in Normal and Pituitary-Grafted Female Rats

Esquifino

Marcó²,

Lafuente³

1994

“…PRL exerts an influence on a number of brain functions [1, 2], such as reproduction [3], sexual behavior [4, 5], feeding behavior [6]and maternal behavior [7]. In addition, PRL acts at the cellular level to regulate GnRH secretion [8, 9, 10], the firing rate of hypothalamic neurons [11], the metabolism of neurotransmitters and neuropeptides [12], oxytocin release [13], enzyme activities in neurons [14]and glial cellular proliferation [15].…”

Section: Introductionmentioning

confidence: 99%

Promoter Usage and Estrogen Regulation of Prolactin Receptor Gene in the Brain of the Female Rat

Zhang²,

Li³

et al. 2003

Mechanisms underlying hormonal regulation of prolactin receptor (PRL-R) gene in the brain are unknown. The 5’-untranslated region of PRL-R mRNA in peripheral tissues contains at least three alternative first exons (1A, B, C) that are expressed as tissue-specific, suggesting the differential usage of PRL-R gene promoters. The present study aimed to investigate: (1) the possible regulation of PRL-R mRNA levels by estrogen in in vitro and in vivo tissues; (2) which exon (1A, or 1B, or 1C)-containing PRL-R mRNA transcript is expressed in the brain, and (3) how the specific exon 1-containing mRNA is affected by estrogen by using RT-PCR, Southern blot and 5’Race PCR techniques. The RT-PCR results showed that PRL-R mRNA was detected in the cerebral cortex and pons medulla in addition to the choroid plexus and hypothalamus in the female rat. The expression of PRL-R mRNA was up-regulated by estrogen treatment in the rat brain tissue and in the GT1-7 cell culture. Both exon 1A- and 1C-containing transcripts were expressed in all four regions, suggesting that promoters 1A and 1C for the PRL-R gene are utilized in the rat brain. Exon 1A-containing transcript was up-regulated by estrogen treatment in all four brain regions, whereas Exon 1C-containing transcript was up-regulated by estrogen treatment in 3 of the 4 brain regions, cerebral cortex being the exception. Exon 1B-containing transcript was neither detectable nor induced by estrogen treatment in any of the brain regions examined. The RT-PCR results were confirmed by partial isolation of 5′-untranslated regions of exon 1A- and 1C-containing PRL-R mRNA transcripts from brain tissue by using 5’Race PCR. The present result confirms the expression of PRL-R mRNA in the cerebral cortex and pons medulla in the female rat. The levels of PRL-R mRNA were up-regulated by estrogen in rat brain tissue and GT1-7 cell cultures. Detection of exon 1A- and 1C-containing transcripts implies that the promoter 1A and 1C are active in the female rat brain. Estrogen differentially regulates expression of the PRL-R mRNA in the different brain regions by increasing the utilization of PRL-R gene promoters 1A and 1C in the female rat.

“…In addition to its diverse effects on peripheral tissues, prolactin (PRL) interacts with the brain [1, 2, 3]to regulate many functions including maternal behavior [4], grooming behavior [5], sexual behavior [6, 7], feeding behavior [8, 9], reproductive function [10]and sleep/wake cycles [11]. The actions of PRL are presumably mediated by the PRL receptor, a membrane-bound receptor which belongs to the cytokine-hematopoietin receptor superfamily [12].…”

Section: Introductionmentioning

confidence: 99%

“…Since PRL has been shown to regulate maternal behavior [4], sexual behavior [6, 7], feeding behavior [8, 9]and reproductive fertility [10], it is suggested that PRL receptors play essential roles in regulating these physiological changes during lactation. It has been reported that the expression of PRL receptor protein is elevated in specific hypothalamic nuclei during lactation when compared with diestrus [25].…”

Section: Introductionmentioning

confidence: 99%

Effect of Suckling on Prolactin Receptor Immunoreactivity in the Hypothalamus of the Rat

Pi¹,

Voogt²

2000

Previous studies showed that expression of prolactin (PRL) receptor is increased in numerous hypothalamic nuclei in mid-lactating rats. The increase in PRL receptor expression could be initated by neurohormonal changes during proestrus or pregnancy, or by the suckling stimulus during lactation. The present study investigated whether the PRL receptor expression in numerous hypothalamic nuclei is altered by the suckling stimulus. Three groups (n = 4) of rats on lactation day 10 were used: a continuously suckled group, a nonsuckled group (pups removed for 12 h) and a resuckled group (pups removed for 12 and then resuckled for 9 h). Animals were perfused with 2% paraformaldehyde and brains were sectioned (20 µm) for the immunofluorescence study. Immunoreactivity was semiquantitatively analyzed by counting the immunoreactive cells and measuring the immunostaining intensity in a specific area. Neurons expressing PRL receptors were observed in numerous hypothalamic areas with the highest number being in the arcuate, paraventricular and supraoptic nuclei. The PRL receptor immunofluorescence in several nuclei was significantly decreased in the nonsuckled group, and recovered in the resuckled group. These areas included the ventromedial preoptic, ventrolateral preoptic, lateroanterior hypothalamic, ventrolateral hypothalamic and ventromedial hypothalamic nuclei. PRL receptor immunoreactivity in other areas was not significantly altered by the suckling stimulus. These results demonstrate that expression of PRL receptor in hypothalamic nuclei was differentially affected by the suckling stimulus. PRL receptors in those nuclei which were significantly altered by suckling stimulus may play more critical roles during lactation than those areas which were less sensitive to the suckling stimulus.