Dopamine control of prolactin secretion

April 25, 2017 by Cleyde Helena, Public Library of Science
This figure shows how TIDA neurons release dopamine at the level of the median eminence. Credit: PLOS Blogs

In women, a major role of prolactin is to initiate and sustain pregnancy and lactation. During pregnancy, prolactin secretion from the pituitary gland is important for pregnancy maintenance and prolactin levels are correlated with miscarriage occurrence. When prolactin levels fail to increase properly, there is a higher risk of miscarriage1. But prolactin levels are also important during the female reproductive cycle – as increased prolactin secretion can cause infertility by inhibiting the release of hormones that trigger ovulation. So prolactin levels cannot be too high to allow ovulation and pregnancy to occur, but also have to increase at a proper rate during early pregnancy to ensure pregnancy success. But how the body carefully regulates prolactin in real time has been a mystery – until now.

Regulation of prolactin secretion

The body controls its hormonal release by means of positive and negative feedback. In a general way, hormones secreted in the hypothalamus (area of the brain that controls the body's homeostasis) stimulate the to secrete several hormones. These hormones enter the blood stream and act in peripheral target glands, stimulating further hormonal release (positive feedback). Subsequently, those hormones secreted by the target glands reach back to where the process started, suppressing hormonal secretion in both hypothalamus and pituitary (negative feedback). Like your home thermostat, sensing when your house is getting too warm, and turning on the air conditioner. Once the optimal temperature is reached, the air conditioner is turned back off.

But is different. It lacks a target peripheral gland, and therefore is not regulated through the standard mechanisms that resemble your thermostat. Unlike other pituitary hormones that are stimulated by the hypothalamus, prolactin secretion is controlled by inhibitory dopaminergic inputs, produced in the tuberoinfundibular region of the hypothalamus (TIDA). We know that dopamine inhibits prolactin (and prolactin in turn, stimulates dopamine), but we do not know the temporal relationship among these players. The activity of dopaminergic neurons is very fast, firing in bursts of spikes happening at 20 seconds intervals2. Prolactin response, in turn, occurs in a much slower way. So how does all this rapid activity of dopaminergic neurons translate into at the median eminence and subsequent (slower) prolactin secretion?

In a recent study published in PNAS, Romano and colleagues used an innovative new approach to investigate real time interaction between dopamine and prolactin. The researchers were able to measure dopaminergic release from TIDA neurons, correlating it to prolactin levels in freely moving mice, in , for several days! They implanted several miniaturized carbon fibers directly into the median eminence of female mice. This area is the part of the hypothalamus where the hormones are released, being the connection between brain and pituitary gland.

There is a hierarchical relationship between different dopaminergic neurons

By analyzing dopaminergic secretion over several days, the authors found that dopamine release was more frequent during the night, and that periods of intense dopaminergic activity were always followed by periods of silence. This makes sense within the feedback nature of the neuroendocrinology system, where hormones are released in pulses, to prevent down-regulation of target receptors. Elevated constant hormonal levels results in a decrease in the quantity of the hormone receptor, resulting in decreased sensitivity (down-regulation).

Analyzing dopaminergic currents on the basis of their shape, the authors realized that the dopaminergic neurons are stereotypically organized in distinct groups, with different and specific firing rates. These stereotypical features of the dopaminergic neurons were consistent between different animals and different days of recording.  When dual-carbon fiber recordings were performed in two distinct 500 μm from each other, the authors discovered that dopaminergic firing events were coordinated within minutes during most of the recordings. Therefore, the activity from all those different TIDA groups is somehow coordinated over a range of minutes before dopaminergic release in the median eminence.

Novel integrated view of how dopamine controls prolactin secretion

Although all TIDA neurons release dopamine in the median eminence, there are different subsets of TIDA neurons, with similar firing patterns among the members of the same group, but not coordinated with other groups (those different TIDA groups are shown in the figure as green, orange, and magenta). Each one of those groups of TIDA follows a stereotyped sequence of events. Meaning that locally, there is an organization of frequencies and the firing events occur as sequences (Short-term interaction). Those local dopaminergic patterns are fine-tuned within pre-established time windows, being totally integrated in the median eminence, before actual dopaminergic release (Long-term interaction).

This type of hierarchical organization of rhythmic activity has been previously seen in several other brain regions, and evolutionarily preserved among several species3. This repetitive rhythmic neural activity generates neural oscillations, which can vary in magnitude and/or frequency. In brain regions with hierarchical organization, several different neuronal oscillators form a linear progression, with slower oscillations regulating the amplitude (size) of the faster ones. This serves as a mechanism to transfer information from large-scale brain networks to the fast, and local cortical, integrating functional systems across multiple spatial and time scales.

This is the first time that a study has been capable to show that the median eminence is capable of integrating hierarchical neuronal oscillating networks, in a specific spatio-temporal pattern. This study opens a whole new path to investigate how hormonal rhythms can occur on multiple time-scales, ranging from minutes and days to seasons, helping to explain slow endocrine events such as reproduction, growth, metabolism, and stress.

Explore further: New principle for brain-controlled hormone secretion

More information: Alison J. Douglas. Baby on board: Do responses to stress in the maternal brain mediate adverse pregnancy outcome?, Frontiers in Neuroendocrinology (2010). DOI: 10.1016/j.yfrne.2010.05.002

David J. Lyons et al. Synchronized Network Oscillations in Rat Tuberoinfundibular Dopamine Neurons: Switch to Tonic Discharge by Thyrotropin-Releasing Hormone, Neuron (2010). DOI: 10.1016/j.neuron.2009.12.024

György Buzsáki et al. Scaling Brain Size, Keeping Timing: Evolutionary Preservation of Brain Rhythms, Neuron (2013). DOI: 10.1016/j.neuron.2013.10.002

Related Stories

New principle for brain-controlled hormone secretion

April 14, 2016
The concentration of the hormone prolactin in the blood is controlled by dopamine. However, the system can be thrown off balance by certain drugs, especially antipsychotics, which can result in sexual side effects. A new ...

Serum prolactin in pregnancy predicts prediabetes / diabetes

May 2, 2016
(HealthDay)—Serum prolactin in pregnancy predicts the risk of postpartum prediabetes/diabetes, according to a study published online April 26 in Diabetes Care.

New insights on control of pituitary hormone outside of brain has implications for breast cancer

October 1, 2012
The hormone prolactin is produced by the pituitary gland in the brain and then travels via the bloodstream to cells throughout the body, where it exerts multiple reproductive and metabolic effects, most notably on the breast ...

Infertility: How can the ovulation function be restored?

October 17, 2012
One of the most frequent is the existence of tumours that induce an over-secretion of this hormone. These women present with chronic infertility due to anovulation. Thanks to the work of the Inserm researchers from unit 693 ...

Recommended for you

New link between sleep arousals and body temperature may also be connected to SIDS

April 25, 2018
Brief arousals during sleep—sometimes as many as ten to fifteen per night—appear random in time and occur in humans and even in animals.

Ethics debate overdue in human brain research: experts

April 25, 2018
What if human brain tissue implanted into a pig transferred some of the donor's self-awareness and memories?

Imaging may allow safe tPA treatment of patients with unwitnessed strokes

April 25, 2018
A study led by Massachusetts General Hospital (MGH) investigators may lead to a significant expansion in the number of stroke patients who can safely be treated with intravenous tPA (tissue plasminogen activator), the "clot ...

Brain structure linked to symptoms of restless legs syndrome

April 25, 2018
People with restless legs syndrome may have changes in a portion of the brain that processes sensory information, according to a study published in the April 25, 2018, online issue of Neurology, the medical journal of the ...

Brain activity linked to stress changes chemical codes

April 24, 2018
Five years ago, a team of University of California San Diego neurobiologists published surprising findings describing how rats' brain cells adopted new chemical codes when subjected to significant changes in natural light ...

Scientists develop new method that uses light to manage neuropathic pain in mice

April 24, 2018
For patients with neuropathic pain, a chronic condition affecting 7 to 8 percent of the European population, extreme pain and sensitivity are a daily reality. There is currently no effective treatment. Scientists from EMBL ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.