Research Into How Hormone Prolactin Is Secreted From The Pituitary Gland

Research Into How Hormone Prolactin Is Secreted From The Pituitary Gland

04 Aug 2010

A Florida State University biologist and mathematician have joined forces to find out exactly how the brain oversees the secretion of the hormone prolactin from the pituitary gland, research that could lead to new ways to treat hundreds of disorders, including infertility.

Marc Freeman, the Lloyd M. Beidler Professor of Biological Science and Distinguished Research Professor Emeritus, and mathematics Professor Richard Bertram have received a $2.64 million, five-year renewal grant from the National Institutes of Health to continue their work. Arturo E. Gonzalez-Iglesias and Joel Tabak-Sznajder, both assistant scholar/scientists in biology at FSU, are working on experimental and mathematical aspects of the project as co-principal investigators.

"We're taking a mathematical approach to answer a biological question," Freeman said, explaining that he and his colleagues have developed a mathematical model to help them find out more about how an important area of the brain, the hypothalamus, oversees the secretion of prolactin. Primarily known for its role in stimulating the mammary gland to produce milk, prolactin actually plays a role in more than 300 functions in addition to those involving reproduction.

The researchers are testing their theory that secretion of prolactin is inhibited by dopamine and stimulated by oxytocin. In addition, the researchers hypothesize that the activities of these neurons are regulated by the hypothalamus and prolactin itself.

"There are two-way interactions here, with the hypothalamus releasing neurohormones like dopamine and oxytocin that act on pituitary cells and the pituitary cells releasing hormones that act on neurons of the hypothalamus," Bertram said. "These hormones and neurohormones are carried by the blood in contrast to communication by the brain itself, which is primarily carried by neurotransmitters released by synapses."

Freeman, who has received continuous NIH funding since 1974 for his research into how the hypothalamus regulates the pituitary gland in the control of reproduction, said it has long been known that dopamine produced by the hypothalamus inhibits prolactin secretion. However, in the case of breastfeeding, a nursing baby will provide enough prolactin-releasing stimuli to inhibit the mother's dopamine so that she can produce prolactin and subsequently breast milk. About 20 years ago, Freeman found that oxytocin could also stimulate prolactin secretion.

Clarifying the role and mechanisms through which oxytocin interacts with dopamine to regulate prolactin secretion has important ramifications for the treatment of disorders, including infertility, related to prolactin's hundreds of biological actions, Freeman said.

For example, the findings could lead to the development of a new way to suppress elevated levels of prolactin that are produced by prolactinomas, which are noncancerous pitituary tumors. Women who have prolactinomas have such high levels of prolactin that it inhibits ovulation and they are unable to conceive. Drugs currently used to treat these tumors have serious negative side effects, Freeman said.

Adding a mathematician to the research team has allowed Freeman to look at his ongoing work from a new angle. He began collaborating with Bertram in 2003, with Bertram writing mathematical equations that simulated Freeman's biological data.

Traditionally, biologists develop a conceptual model of how things interact and use this conceptual model to design and interpret experiments, Bertram explained. Typically, this is a verbal model, complemented with a "box-and-arrows" diagram showing the biological players and their interactions. A mathematical model converts the diagram into differential equations, which describe how things affect each other and change over time.

"With a mathematical model, it is much easier to see if hypotheses can possibly work, and to make predictions that can be tested in the lab," Bertram said. "Another benefit of the mathematical model is that it points out missing information - things that are required for the equations but are often overlooked in box-and-arrows diagrams."

Source: Florida State University

Article URL: http://www.medicalnewstoday.com/articles/196713.php

Quinagolide - a valuable treatment option for hyperprolactinaemia -- Barlier and Jaquet

Quinagolide - a valuable treatment option for hyperprolactinaemia -- Barlier and Jaquet 154 (2): 187 -- European Journal of Endocrinology

CAB doesn't seem to be getting the PRL level down as much as we'd like, even at 0.75mg x 4/week. We're considering switching to QUI (Quinagolide). QUI appears to offer similar effectiveness in most studies. In addition, it's not an ergot-derived drug, so it should not have some of the risks that Bromocriptine and CAB have.

Treating pituitary tumors

Stress Hormone Key To Alcohol Dependence

Stress Hormone Key To Alcohol Dependence

A team of scientists from The Scripps Research Institute has found that a specific stress hormone, the corticotropin-releasing factor (CRF), is key to the development and maintenance of alcohol dependence in animal models. Chemically blocking the stress factor also blocked the signs and symptoms of addiction, suggesting a potentially promising area for future drug development...

"I'm excited about this study," said Associate Professor Marisa Roberto, who led the research. "It represents an important step in understanding how the brain changes when it moves from a normal to an alcohol-dependent state."

The new study not only confirms the central role of CRF in alcohol addiction using a variety of different methods, but also shows that in rats the hormone can be blocked on a long-term basis to alleviate the symptoms of alcohol dependence.

CRF is a natural substance involved in the body's stress response. Originally found only in the area of the brain known as the hypothalamus, it has now been localized in other brain regions, including the pituitary, where it stimulates the secretion of corticotropin and other biologically active substances, and the amygdala, an area that has been implicated in the elevated anxiety, withdrawal, and excessive drinking associated with alcohol dependence...

The results from these cellular studies showed that CRF increased the strength of inhibitory synapses (junctions between two nerve cells) in neurons in a manner similar to alcohol. This change occurred through the increased release of the neurotransmitter GABA, which plays an important role in regulating neuronal excitability...

Roberto notes that another intriguing aspect of the work is that it provides a possible physiological link between stress-related behaviors, emotional disorders (i.e. stress disorders, anxiety, depression), and the development of alcohol dependence.

Cabergoline dosage

"Tumors of the pituitary gland and other hyperprolactinemic conditions: Initially 0.5 mg per week, slowly titrated to 4.5 mg per week, if necessary." -Wikipedia

"For disorders of high prolactin levels or pituitary tumors: Adults—0.25 milligram (mg) two times a week. Dose may be increased every four weeks as needed, according to body prolactin levels, up to 1 mg two times a week." -MayoClinic.com

Aneeve To Develop Sensors To Monitor Hormone Levels For Menopause, Fertility

Aneeve To Develop Sensors To Monitor Hormone Levels For Menopause, Fertility

Aneeve's primary research focus within the incubator will be to develop a consumer-based, simple-to-use meter for sensing estrogen and progesterone hormone levels to assist women in mitigating unwanted symptoms of menopause. The meter will provide on-demand hormonal levels so patients can better control drug intake related to hormone therapy. The system is intended to be low cost, compact and easy to use. Currently, there is no such meter commercially available.

How about prolactin and dopamine, too?

Pituitary imaging

Sella Turcica and Parasellar Region -by Walter Kucharczyk and Marieke Hazewinkel

Presentation: "Pituitary Imaging" -Elias Melhem, M.D.

Cabergoline background

Prolactinomas Resistant to Standard Dopamine Agonists Respond to Chronic Cabergoline Treatment

Constant headache

Why the constant headache?

• It doesn't seem to be caused by prolactinemia, because Pat has constant headache that does not seem correlated to her prolactin level... although her PRL level never drops below about 30.
  
• It doesn't seem to be caused by the Cabergoline treatment, because when Pat's CAB treatment has been discontinued for a month or two at a time the headache persists.
  
• Can headache result from distortion of the diaphragma sellae caused by intracranial pressure in patients with secondary empty sella syndrome?

Learning about pituitary disorders

Empty Sella Syndrome -Munir Ahmad Elias, M.D., PhD., Neurosurgeon.

Presentation: "Focus on the Pituitary" -Ariel Barkan, M.D. June 15, 2004)

Presentation: "Pituitary Imaging" -Elias Melhem, M.D.

Hyperprolactinemia -Anne Klibanski, MD and Janet A. Schlechte, MD

Researchers discover GnIH (Gonadotropin Inhibitory Hormone)

New Human Reproductive Hormone Could Lead To Novel Contraceptives And New Cancer Treatments

[Researchers] showed that the hormones are present in a region of the brain, the hypothalamus, that controls reproduction. In addition, GnIH affects nerve cells that secrete GnRH, which is in line with previous findings that GnIH down-regulates GnRH.

Finally, they found that the hypothalamus and pituitary - two key parts of the reproductive axis in the brain have receptors for the hormones.

..."GnIH pushes the pause button on reproduction, but in a variety of ways," Bentley said. "It can act on GnRH neurons in the hypothalamus, inhibiting GnRH release; it can act directly on pituitary; or it can influence the gonads directly. The overall effect is to inhibit reproduction, but at different levels of the reproductive axis."

Purpose of Pituitary Post

The blog is intended to collect information related to a condition experienced by a person (identified in this blog as a female in her teens, named "Pat"). Pat's situation can be described briefly as follows:

• Hyperprolactinemia, pituitary macroadenoma diagnosed around age 10;
• Treatment with Cabergoline quickly shrank adenoma, but now empty sella in indicated;
• Prolactin remains high, and is only partially controlled with Cabergoline;
• Chronic, constant headache.

DISCLAIMER

The author of this blog is not a physician or medical professional.

The contents of this blog are personal notes that in no way constitute medical advice.