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Modulation of prolactin secretion in human myometrium by cytokines
1Institute for Hormone and Fertility Research, Hamburg, Germany.
Abstract:
Prolactin (PRL) secretion and PRL mRNA expression in human myometrial explant cultures was inhibited by the addition of human placental conditioned medium (HPCM). After 3 days treatment with 5% HPCM PRL secretion was reduced to 24% of control values (P < 0.001). The effect persisted even after removal of progesterone, which suppresses myometrial PRL production, from the HPCM. In search for additional regulatory substances present in the uteroplacental unit, we tested a number of growth factors and cytokines known to affect pituitary PRL secretion. Treatment with endothelin-3 (ET-3) at a dose of 10(-6) M was found to increase PRL release by 20% over 3 days (P < 0.05) whereas interleukin-6 (IL-6) showed no effect on PRL levels. Epidermal growth factor, vasoactive intestinal peptide and interferon-alpha (IFN-alpha) were inhibitory. Interleukin-4 (IL-4) was the most potent inhibitor of PRL expression in myometrial tissue, causing a reduction of secreted PRL to less than 50% of controls after 3 days at a dose of > or = 5 ng/ml (P < 0.001) and a concomitant reduction of PRL mRNA levels. These results demonstrate a modulation of PRL expression in the myometrium by locally present factors.
Insights
Human placental conditioned medium (HPCM) inhibits prolactin (PRL) secretion and mRNA expression in myometrial tissue. Interleukin-4 (IL-4) is a potent inhibitor, demonstrating local regulation of PRL by uteroplacental factors.
Area of Science:
- Reproductive Endocrinology
- Molecular Endocrinology
- Uterine Physiology
Background:
- Prolactin (PRL) plays a role in uterine function.
- The regulation of PRL in the myometrium is not fully understood.
- The uteroplacental unit may produce factors influencing myometrial PRL.
Purpose of the Study:
- To investigate the effect of human placental conditioned medium (HPCM) on myometrial prolactin (PRL) secretion and mRNA expression.
- To identify specific factors within HPCM that modulate myometrial PRL.
- To explore the local regulation of PRL in the human myometrium.
Main Methods:
- Human myometrial explant cultures were treated with HPCM.
- PRL secretion was measured using established assays.
- PRL mRNA levels were assessed.
- Specific growth factors and cytokines (ET-3, IL-6, EGF, VIP, IFN-α, IL-4) were tested individually.
Main Results:
- HPCM significantly inhibited PRL secretion and mRNA expression in myometrial explants.
- The inhibitory effect of HPCM persisted even after progesterone removal.
- Interleukin-4 (IL-4) was identified as a potent inhibitor, reducing PRL secretion and mRNA levels.
- Endothelin-3 (ET-3) showed a modest increase in PRL release, while IL-6 had no effect.
Conclusions:
- Local factors within the uteroplacental unit, such as IL-4, modulate PRL expression in the human myometrium.
- These findings suggest a paracrine/autocrine regulation of PRL in the myometrium.
- The study highlights the complex interplay of factors regulating uterine function during pregnancy.