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Regulation of prolactin receptor gene expression by thyroid hormone status in the rat
T S Tiong1, J L Stevenson, A C Herington
1Prince Henry's Institute of Medical Research, Monash Medical Centre, Melbourne, Victoria, Australia.
Abstract:
The nature and tissue distribution of prolactin receptor (PRL-R) mRNA in both male and female rats was studied. A single mRNA species of 2.2 kb was identified in the liver, kidney, adrenal, prostate, lactating mammary gland and ovary but not in the male lung, heart, skeletal muscle, thymus, adipose tissue or brain. There were distinct and contrasting sex differences in abundance of PRL-R mRNA in some tissues: liver (female much greater than male), kidney and adrenal (male much greater than female). A mRNA species of 4 kb was occasionally detected in the male adrenal and female liver. Given previous reports on the effects of thyroid status on PRL binding, the effects of thyroxine (T4), propylthiouracil (PTU) or combined treatment on PRL-R mRNA were assessed. In the male rat, PTU treatment markedly increased (three- to fourfold) PRL-R mRNA in the liver but decreased it (approximately 50%) in the kidney. These changes were reflected in similar changes in lactogenic binding activity. T4 or PTU treatment increased PRL-R mRNA in the prostate, with no obvious changes in binding. No major changes were seen in adrenal glands. In the female rat, PTU had little effect on PRL-R mRNA in any tissue, although binding of 125I-labelled lactogen was decreased in both the liver and kidney. There was an unexpected threefold rise in PRL-R mRNA in the female kidney following combined T4 and PTU treatment. Overall, there was a quite close correlation between the effects of thyroid status on PRL-R mRNA levels and specific lactogenic binding to membranes prepared from the same tissue samples. These studies provide data on the tissue distribution and size of PRL-R mRNA in rats and suggest a novel and complex tissue- and sex-dependent regulation by thyroid hormone.
Insights
This study maps prolactin receptor (PRL-R) mRNA distribution in rats, revealing sex-specific differences and thyroid hormone regulation. PRL-R mRNA levels and binding activity closely correlate with thyroid status, indicating complex hormonal control.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Prolactin receptor (PRL-R) plays a crucial role in mediating prolactin's diverse physiological effects.
- Understanding PRL-R mRNA tissue distribution and regulation is essential for deciphering prolactin signaling pathways.
- Previous studies suggested a link between thyroid status and prolactin binding, but the molecular basis remained unclear.
Purpose of the Study:
- To investigate the tissue distribution and size of prolactin receptor (PRL-R) mRNA in male and female rats.
- To examine the influence of thyroid hormones (thyroxine and propylthiouracil) on PRL-R mRNA expression and lactogenic binding.
- To elucidate the sex- and tissue-specific regulation of PRL-R mRNA by thyroid status.
Main Methods:
- Northern blot analysis was used to detect and quantify PRL-R mRNA species in various rat tissues.
- Specific binding assays with 125I-labelled lactogen were performed to measure lactogenic binding activity.
- Rats were treated with thyroxine (T4) and/or propylthiouracil (PTU) to modulate thyroid hormone levels.
Main Results:
- A 2.2 kb PRL-R mRNA species was found in liver, kidney, adrenal, prostate, mammary gland, and ovary, with distinct sex differences in abundance (e.g., higher in female liver, higher in male kidney/adrenal).
- Thyroid manipulation significantly altered PRL-R mRNA levels and lactogenic binding, particularly in male rats (PTU increased liver mRNA, decreased kidney mRNA).
- A close correlation was observed between changes in PRL-R mRNA levels and lactogenic binding activity following thyroid hormone treatment.
Conclusions:
- PRL-R mRNA exhibits a specific tissue distribution in rats, with notable sex-dependent variations.
- Thyroid hormones exert a complex, tissue- and sex-specific regulatory effect on PRL-R mRNA expression and function.
- These findings highlight a novel mechanism of PRL-R regulation by thyroid status, impacting prolactin signaling.