Prolactin - another obesity hormone

[Taka]

High prolactin levels due to a pituitary tumor or sleep
disturbances may be another cause of the metabolic syndrome,
insulin resistance and subsequently heart disease. The effects
resemble low thyroid.

Pituitary. 2008 Mar 13. [Epub ahead of print]

The effects of hyperprolactinemia on bone and fat.

Shibli-Rahhal A, Schlechte J. Department of Internal Medicine,
University of Iowa Hospitals and Clinics, Iowa City, IA,
52242, USA.

Many patients with prolactin secreting pituitary tumors have
decreased bone mineral. The bone loss is associated with an
increase in bone resorption and is secondary to
prolactin-induced hypogonadism. In both sexes trabecular bone
in the spine and hip is more affected than cortical bone in
the distal radius. Normalization of prolactin and restoration
of gonadal function increases bone density but is not
associated with normalization of bone mass. It is not known
whether the bone loss in hyperprolactinemic subjects
represents a failure to achieve peak bone mass or is due to
accelerated bone loss. Despite low bone density
hyperprolactinemic subjects do not demonstrate increased
fractures. The association between prolactin, weight gain and
obesity suggests that prolactin may also be a modulator of
body composition and body weight. It is not known whether
hyperprolactinemia associated weight gain is due to
stimulation of lipogenesis or due to disruption of central
nervous system dopaminergic tone. Hyperprolactinemia is also
associated with insulin resistance and endothelial dysfunction
which may improve after normalization of prolactin. The
clinical significance of these findings and the precise role
of prolactin in regulation of weight and metabolism remain to
be elucidated. PMID: 18338266

Diabetes Obes Metab. 2007 Jul;9(4):464-76.

Adipocyte prolactin: regulation of release and putative
functions.

Brandebourg T, Hugo E, Ben-Jonathan N. Department of Cell
Biology, University of Cincinnati School of Medicine,
Cincinnati, OH, USA.

Pituitary-derived prolactin (PRL) is a well-known regulator of
the lactating mammary gland. However, the recent discovery
that human adipose tissue produces PRL as well as expresses
the PRL receptor (PRLR) highlights a previously unappreciated
action of PRL as a cytokine involved in adipose tissue
function. Biologically active PRL is secreted by all adipose
tissue depots examined: breast, visceral and subcutaneous. The
expression of adipose PRL is regulated by a non- pituitary,
alternative superdistal promoter. PRL expression and release
increases during early pre-adipocyte differentiation and is
stimulated by cyclic AMP activators, including beta adrenergic
receptor agonists. PRL release from subcutaneous adipose
explants is attenuated during obesity, suggesting that adipose
PRL production is altered by the metabolic state. Several
lines of evidence indicate that PRL suppresses lipid storage
as well as the release of adipokines such as adiponectin,
interleukin-6 and possibly leptin. PRL has also been
implicated in the regulation of adipogenesis. A newly
developed PRL-secreting human adipocyte cell line, LS14,
should allow comprehensive examination of the regulation and
function of adipocyte- derived PRL. Collectively, these
studies raise the prospect that PRL affects energy homeostasis
through its action as an adipokine and is involved in the
manifestation of insulin resistance. PMID: 17587388

Taka

[Taka]

And it looks AA is at play here as well:

Comp Biochem Physiol A Mol Integr Physiol. 2007
Apr;146(4):470-4. Epub 2006 Feb 20.

Fatty acid profiles in hepatic membranes of rats with
different levels of circulating estrogen and prolactin.

Bellini MJ, Carino MH, Tacconi-G=F3mez Dumm N, Goya RG.
Instituto de Investigaciones Bioqu=EDmicas de La Plata
(INIBIOLP-CONICET- UNLP), Argentina.

Plasma and liver microsomal fatty acid patterns of female rats
(Rattus norvegicus) with either low or high serum levels of
prolactin (PRL) were studied. Hyperprolactinemia was achieved
by grafting anterior pituitary glands or by estradiol
administration. One group treated with estradiol also received
bromocriptine to inhibit PRL secretion. Ovariectomized (OVX)
rats showed a decrease in PRL levels as compared with intact
animals (controls). Rats possessing high levels of circulating
PRL showed a significant decrease of linoleic acid in the
fatty acid pattern of total and polar liver microsomal lipids.
High PRL levels in the presence of normal estrogen levels
significantly increased arachidonic acid in the same group of
lipids. The group of rats treated with estrogen evidenced a
decrease in arachidonic acid and in the unsaturation index.
From these results it is possible to infer a decrease in the
activity of the desaturases. The changes observed in the
estradiol-treated group were not modified by bromocriptine
administration. OVX rats showed no changes when compared with
controls. It is concluded that, while PRL decreases the
microsomal unsaturation index, estrogen administration causes
a decrease in poly-unsaturated fatty acid biosynthesis and
that this effect is independent of PRL levels. PMID: 16490375

Results Probl Cell Differ. 2008;46:57-88.

Prolactin-releasing Peptide.

Lin SH. Department of Radiation Oncology and Molecular
Radiation Sciences,Sydney Kimmel Comprehensive Cancer Center,
The Johns Hopkins Hospital, 401 North Broadway Avenue, Suite
1440, 21231, Baltimore, MD, USA,

Prolactin-releasing peptide (PrRP) was initially isolated from
the bovine hypothalamus as an activating component that
stimulated arachidonic acid release from cells stably
expressing the orphan G protein-coupled receptor hGR3 (Hinuma
et al. 1998) [also known as GPR10 (Marchese et al. 1995), or
UHR-1 for the rat orthologue (Welch et al. 1995)]. Initially
touted as a prolactin-releasing factor (therefore aptly named
prolactin-releasing peptide), the perspective on the function
of this peptide in the organism has been greatly expanded.
Over 120 papers have been published on this subject since its
initial discovery in 1998. Herein I review the state of
knowledge of the PrRP system, its putative function in the
organism, and implications for therapy. PMID: 18204826

[Taka]

Now let's see how we can decrease the prolactin (PRL) release
- "the capacity to release PRL was markedly decreased in
EFA-deprived cells":

Neuroendocrinology. 1994 Oct;60(4):400-9.

Selective effect of a diet-induced decrease in the arachidonic
acid membrane-phospholipid content on in vitro phospholipase C
and adenylate cyclase-mediated pituitary response to
angiotensin II.

Al=E9ssio ML, L=E9ger CL, Rasolonjanahary R, Wandscheer DE,
Clauser H, Enjalbert A, Kordon C. INSERM U-159, Unit=E9 de
Neuroendocrinologie, Centre Paul-Broca, Paris, France.

Young rats were fed on an essential fatty acid (EFA)-deprived
diet for 6 weeks after weaning. Their pituitary was removed
and adenohypophyseal cells dispersed and maintained in
culture. Membrane lipids were analyzed and basal and
stimulated levels of hormone secretion were measured after
4-day incubation in a culture medium containing or not 160
microM arachidonic acid 20:4n-6 (AA) in order to obtain
EFA-deficient or EFA-restored pituitary cells, respectively.
In EFA-deficient cells membrane phosphoglycerides (PGL) were
depleted in AA and adrenic acid 22:4n-6; the deficit was
overcome by incubation in the presence of AA. Depletion
diversely affected PGL classes. AA was highly depleted in
choline phosphoglycerides (ChoPG), only moderately depleted in
serine and ethanolamine phosphoglycerides (SerPG and EtnPG)
and not depleted at all in inositol phosphoglycerides,
suggesting preferential preservation of AA in that class of
PGL. Restoration of AA by addition of the fatty acid to the
culture medium was complete for ChoPG and EtnPG and only
partial for SerPG. Depressed levels of AA and adrenic acid in
PGL were compensated for by a concomitant increase in 20:3n-9
and 22:3n-9. Growth hormone and prolactin (PRL) secretion was
assessed by radioimmunoassay and possible effects of a
membrane AA deficit on hormone regulation were tested in cells
challenged by either growth hormone-releasing hormone,
thyrotropin-releasing hormone, angiotensin II (AII),
vasoactive intestinal peptide (VIP) or dopamine. Neither basal
nor stimulated growth hormone secretion was different from
controls in EFA-deficient cells. PRL modulation by VIP or
dopamine was not affected either in EFA-deficient cells. In
contrast, the capacity of AII, but not of
thyrotropin-releasing hormone, to release PRL was markedly
decreased in EFA-deprived cells. It was restored by addition
of AA to the incubation medium. Parallel depression of
AII-induced inositol phosphates and cAMP accumulation was also
observed after EFA deficiency. When tested on membranes, the
paradoxical inhibition of adenylate cyclase by AII documented
by previous observations was reinforced in EFA-deficient
membranes. In contrast, binding of AII was not affected by EFA
deficiency. It is concluded that under our experimental
conditions EFA deficiency affects selectively coupling of the
AII receptor to its effectors without alteration of binding.
The effect could involve changes in receptor interactions with
coupling proteins. PMID: 7824082

Endocrinology. 1988 Nov;123(5):2445-53.

The dynamics of arachidonic acid liberation and prolactin
release: a comparison of thyrotropin-releasing hormone,
angiotensin II, and neurotensin stimulation in perifused rat
anterior pituitary cells.

Ross PC, Judd AM, MacLeod RM. Department of Internal
Medicine, University of Virginia School of Medicine,
Charlottesville 22908.

The dynamics of arachidonic acid (AA) liberation and PRL
release were highly correlated in perifused rat anterior
pituitary cells during stimulation by three different
neuropeptides: TRH, angiotensin II (AII), and neurotensin
(NT). After preincubation of these cells with 1 microCi
[3H]AA, a 20-min perifusion with AII (100 nM), TRH (100 nM),
or NT (1 microM) elicited a sharp initial increase in PRL
release and
[3H]AA efflux, which rapidly subsided (within 6 min) to
less elevated levels of PRL release and AA liberation.
The plateau responses were sustained throughout the
remainder of the 20-min treatment period; after the
cessation of neuropeptide perifusion, the responses
rapidly returned to basal levels. AII and TRH elicited
a greater initial stimulation of PRL release and AA
liberation, whereas NT resulted in less pronounced
initial responses and a greater plateau of sustained
PRL release and AA liberation. Dopamine (DA; 500 nM) or
calcium- depleted medium (containing 60 microM EGTA)
evenly attenuated the stimulation of PRL release
throughout exposure to the neuropeptides; however, the
initial stimulation of AA efflux by AII and TRH was
relatively resistant to inhibition by DA or
calcium-depleted medium. In contrast, the stimulation
of AA liberation by NT was abolished by DA or
calcium-dependent medium. These results establish that
the time course of AA liberation is complimentary to
that of PRL release during stimulation by AII, TRH, and
NT and support a possible role for AA liberation and
metabolism as one of the mechanisms that participates
in the regulation of PRL release. A lesser ability of
NT to elicit functional and biochemical responses to
intracellular calcium mobilization is postulated as an
explanation for the observed differences among AII,
TRH, and NT effects on PRL release and AA liberation.
PMID: 3139397

[Taka]

Life Sci. 1993;52(24):1977-84.

Effects of specific fatty acids on prolactin-induced NB2
lymphoma cell proliferation.

Sylvester PW, Ip MM, Briski KP. Hormonal Carcinogenesis
Laboratory, College of Pharmacy, Washington State University,
Pullman 99164-6510.

Nb2 rat lymphoma cells are dependent on prolactin (PRL) for
growth. Membrane lipid composition of Nb2 cells undergoes
rapid modification when these cells are grown in culture media
supplemented with specific fatty acids. Since the actions of
PRL are mediated through specific membrane receptors, the
following studies were conducted to characterize the
lipid-dependent events involved in fatty acid modulation of
PRL-induced cell proliferation. Nb2 cells were grown in
suspension cultures in control or fatty acid-supplemented
media, in the presence of various doses of PRL. PRL-induced
cell growth was significantly enhanced by arachidonate, but
significantly attenuated by stearate supplementation of the
culture media. A direct relationship was observed between the
concentration of specific fatty acid added to the culture
media and the magnitude with which this fatty acid was
incorporated into Nb2 cell membranes, as determined by gas
chromatography. Acute treatment with phorbol ester enhanced
Nb2 cell growth in control media and reversed the attenuating
effects of membrane stearic acid enrichment. However,
PRL-induced Nb2 cell growth was similar with or without the
presence of phorbol ester, when cells were grown in media
supplemented with arachidonate. Addition of protein kinase C
(PKC) inhibitors to control and fatty acid- supplemented media
resulted in a dose-dependent inhibition of PRL- induced Nb2
cell proliferation. These results suggest that lipid
modulation of Nb2 mitogenic-responsiveness to PRL is mediated
through alterations in PKC activation. PMID: 8505862

[Taka]

On May 25, 1:13 am, Taka <taka0...@gmail.com> wrote:
> Now let's see how we can decrease the prolactin (PRL)
> release - "the capacity to release PRL was markedly
> decreased in EFA-deprived cells":

Eicosanoids. 1992;5(3-4):153-61.

Prolactin secretion in anterior pituitary cells: effect of
eicosanoids.

Cashman JR, Snowdowne KW. Department Pharmaceutical Chemistry
School of Pharmacy, University of California San Francisco
94143-0446.

Ovariectomized Fischer 344 rats were implanted with silastic
capsules containing estradiol for approximately 4 weeks to
increase the number of lactotrophs in the anterior pituitary
gland. Anterior pituitary cells were enzymatically dispersed
and cultured for 1 day and challenged with eicosanoids or
other prolactin (PRL) secretagogues. The isolated pituitary
cells from estradiol-pretreated animals exhibited an increase
in the ability to secrete PRL in the presence of maximally
effective concentrations of thyrotropin releasing hormone
(TRH), arachidonic acid or 5,6-epoxyeicosatrienoic acid
(5,6-EET). Anterior pituitary cells from estradiol-pretreated
animals also showed an increased activity of cytochrome P-450.
The possible involvement of cytochrome P-450 in PRL secretion
from anterior pituitary animal cells isolated from animals
pretreated with estradiol was shown by the fact that these
anterior pituitary cells increased the synthesis of 5,6- EET,
a potent PRL releasing agent. TRH and 5,6-EET increased the
mobilization of both cyclic AMP and cytoplasmic calcium to
about the same extent. The data suggest that cytochrome P-450
is important in the release of PRL from anterior pituitary
cells isolated from estradiol-pretreated Fischer 344 rats and
that a product of cytochrome P-450-catalyzed epoxidation of
arachidonic acid, 5,6-EET, plays a significant role in the
release of PRL. PMID: 1337974

Neuroendocrinology. 1987 Sep;46(3):246-51.

Epoxy derivatives of arachidonic acid are potent stimulators
of prolactin secretion.

Cashman JR, Hanks D, Weiner RI. Department of Pharmaceutical
Chemistry, University of California, San Francisco.

Arachidonic acid is metabolized to three distinct classes of
metabolites: cyclooxygenase produces prostaglandins,
prostacyclins, and thromboxanes; lipoxygenase produces
hydroperoxyeicosatetraenoic acids and, epoxygenase, a
NADPH-dependent cytochrome P-450 enzyme, produces
epoxyeicosatrienoic acids. Addition of 5,6-
epoxyeicosatrienoic acid (5,6-EET) to GH3 cells, a rat
anterior pituitary cell line, produces a rapid, dose-dependent
stimulation of prolactin (PRL) release. Incubation with
arachidonic acid (AA) was ineffective at increasing PRL
release. The lipoxygenase metabolite 5-
hydroxyeicosatetraenoic acid (5-HETE), however, increased PRL
release from GH3 cells but with a much lower maximal response
than 5,6-EET. We examined the role of metabolism inhibitors in
5,6-EET-mediated PRL release. Microsomal and cytosolic epoxide
hydrolase (EH) inhibitors do not alter 5,6-EET-induced PRL
release, suggesting that EH does not play a significant role
in 5,6-EET mediated PRL release from GH3 cells. A chemical
analog of 5,6-EET wherein the epoxide oxygen is replaced with
a sulfur to afford 5,6-thioepoxyeicosatrienoic acid was also
tested and found to stimulate the release of PRL, although not
to the same extent as 5,6-EET. Although 5-HETE tends to
increase PRL release from GH3 cells, 5,6-EET is significantly
more potent at the stimulation of PRL release from GH3 cells.
PMID: 3658112

[Marshall P]

Taka wrote:
> High prolactin levels due to a pituitary tumor or sleep
> disturbances may be another cause of the metabolic syndrome,
> insulin resistance and subsequently heart disease. The
> effects resemble low thyroid.
>
> Pituitary. 2008 Mar 13. [Epub ahead of print]
>
> The effects of hyperprolactinemia on bone and fat.
>
> Shibli-Rahhal A, Schlechte J. Department of Internal
> Medicine, University of Iowa Hospitals and Clinics, Iowa
> City, IA, 52242, USA.
>
> Many patients with prolactin secreting pituitary tumors have
> decreased bone mineral. The bone loss is associated with an
> increase in bone resorption and is secondary to
> prolactin-induced hypogonadism. In both sexes trabecular
> bone in the spine and hip is more affected than cortical
> bone in the distal radius. Normalization of prolactin and
> restoration of gonadal function increases bone density but
> is not associated with normalization of bone mass. It is not
> known whether the bone loss in hyperprolactinemic subjects
> represents a failure to achieve peak bone mass or is due to
> accelerated bone loss. Despite low bone density
> hyperprolactinemic subjects do not demonstrate increased
> fractures. The association between prolactin, weight gain
> and obesity suggests that prolactin may also be a modulator
> of body composition and body weight. It is not known whether
> hyperprolactinemia associated weight gain is due to
> stimulation of lipogenesis or due to disruption of central
> nervous system dopaminergic tone. Hyperprolactinemia is also
> associated with insulin resistance and endothelial
> dysfunction which may improve after normalization of
> prolactin. The clinical significance of these findings and
> the precise role of prolactin in regulation of weight and
> metabolism remain to be elucidated. PMID: 18338266
>
>
> Diabetes Obes Metab. 2007 Jul;9(4):464-76.
>
> Adipocyte prolactin: regulation of release and putative
> functions.
>
> Brandebourg T, Hugo E, Ben-Jonathan N. Department of Cell
> Biology, University of Cincinnati School of Medicine,
> Cincinnati, OH, USA.
>
> Pituitary-derived prolactin (PRL) is a well-known regulator
> of the lactating mammary gland. However, the recent
> discovery that human adipose tissue produces PRL as well as
> expresses the PRL receptor (PRLR) highlights a previously
> unappreciated action of PRL as a cytokine involved in
> adipose tissue function. Biologically active PRL is secreted
> by all adipose tissue depots examined: breast, visceral and
> subcutaneous. The expression of adipose PRL is regulated by
> a non- pituitary, alternative superdistal promoter. PRL
> expression and release increases during early pre-adipocyte
> differentiation and is stimulated by cyclic AMP activators,
> including beta adrenergic receptor agonists. PRL release
> from subcutaneous adipose explants is attenuated during
> obesity, suggesting that adipose PRL production is altered
> by the metabolic state. Several lines of evidence indicate
> that PRL suppresses lipid storage as well as the release of
> adipokines such as adiponectin, interleukin-6 and possibly
> leptin. PRL has also been implicated in the regulation of
> adipogenesis. A newly developed PRL-secreting human
> adipocyte cell line, LS14, should allow comprehensive
> examination of the regulation and function of adipocyte-
> derived PRL. Collectively, these studies raise the prospect
> that PRL affects energy homeostasis through its action as an
> adipokine and is involved in the manifestation of insulin
> resistance. PMID: 17587388
>
> Taka

What are subcutaneous adipose explants?

--
Marshall Price of Miami Known to Yahoo as d021317c