Prolactin and Growth Hormone

Author: Gianpiero Pescarmona
Date: 01/04/2009



A short protein description with the molecular wheight, isoforms, etc...
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Normal Prolactin Levels in Breastfeeding Mothers


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  • Primary structure
  • Secondary structure
  • Tertiary structure
  • Quaternary structure

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  • Cell signaling and Ligand transport

Non-genomic and genomic effects of Prolactin

Nuclear localization and function of polypeptide ligands and their receptors: a new paradigm for hormone specificity within the mammary gland? 2003

Papers Skin Prolactin

Pregnancy hormones boost beta cells via serotonin 2010

Papers BH4 Prolactin

Treatment of BH4 deficiency, i.e. BH4, 5-hydroxytryptophan, and L-DOPA/carbidopa (the last named given in three doses per day), suppresses prolactin levels merely for a few hours. L-DOPA/carbidopa given at shorter intervals or, even better, as a slow release preparation, is more effective in suppressing prolactin levels. Our data indicate immense hyperprolactinemia but few other hormonal disturbances

Prolactin is primarily under tonic inhibitory control by the hypothalamus through the release of dopamine (DA). Several prolactin-releasing factors (PRFs) have been identified in the hypothalamus that may play a role under certain conditions such as suckling or stress. In the case of suckling (or breast stimulation), tonic inhibition of prolactin secretion is overridden by neurogenetic signals from the breast through a multisynaptic pathway that stimulates PRF and inhibits dopamine. Estrogen also induces hyperplasia and hypertrophy of prolactin cells and increases prolactin secretion.

additional data

Schematics representing the pathways through which serotonin may stimulate PRL secretion. See text for details. PVN, paraventricular nucleus; MFB, medial forebrain bundle; F, fornix; PRL, prolactin; ARC, arcuate nucleus; DA, dopamine; PRF, prolactin-releasing factor; VIP, vasoactive intestinal peptide; OT, oxytocin; TIDA, tuberoinfundibular dopamine pathway; OC, optic chiasm; 5-HT, serotonin; GABA, gamma-aminobutyric acid.

From Galactorrhea to Osteopenia: Rethinking Serotonin–Prolactin Interactions 2004

Dopamine - RED / Prolactin - BLUE dopamine drops, prolactin rises Research shows that prolactin surges immediately after orgasm in both men and women. Men may experience this prolactin surge as the "roll over and snore" phenomenon. In women, the effects may be delayed for days. We notice that the effects come and go for about two weeks.

There’s an inverse relationship between the levels of prolactin and dopamine; when one is up the other is down. This rise and fall may produce a dopamine/prolactin roller coaster of highs and lows. We suspect that prolactin, and this roller coaster, are aspects of the post-orgasm hangover.

Notice that in women excess prolactin is also associated with anxiety and hostility. Sound familiar? The following table lists symptoms of patients with chronically elevated prolactin. We think that after sex, prolactin surges may be subtle, but still noticeable in their effects. The symptoms could be due to the rises in prolactin or the consequent suppression of dopamine.

Women Men
Loss of libido Loss of libido
Mood changes / depression Mood changes / depression
Hostility, anxiety Impotence
Headache Headache

A possible role for lipoxygenase and epoxygenase arachidonate metabolites in prolactin release from pituitary cells. 1988

Therefore, the production of leukotrienes, HETEs, and epoxyeicosatrienoic acids may be necessary for the normal release of prolactin.

Angiotensin increases arachidonate metabolism in cultured anterior pituitary cells. 1989

The inhibitor of the cyclo-oxygenase pathway, indomethacin, did not significantly modify angiotensin II-induced prolactin release, whereas BW 755c and ETYA (inhibitors of cyclo-, lipo- and epoxygenase pathways) and NDGA (an inhibitor of leukotriene and epoxyeicosanoid synthesis) completely counteracted the effect of the octapeptide on hormone release.

Signs of increased testosterone levels Decreased testosterone levels


more at wellsphere.....


Hyperprolactinemia treatment

bromocriptina mesilato 2,87 mg, pari a 2,5 mg di bromocriptina base.
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Prolactin blocks nuclear translocation of VDR by regulating its interaction with BRCA1 in osteosarcoma cells. 2009

Prolactin and BRCA1

  • Structural proteins


Androsterone etiocolanone alti

Effects of sulpiride on levels of FSH, LH and steroid hormones. 1984

  • In order to study the effects of prolactin upon the gonadotrophins and steroid hormones, hyperprolactinaemia was induced by the administration of sulpiride. 12 men between the ages of 18 and 20 were given 3 capsules of 50 mg of sulpiride daily for a period of 15 days, and the following parameters being measured before and after the treatment: (prolactine, FSH, LH, testosterone, estradiol, ACTH and DHEA-S) by RIA, (cortisol) by fluorimetry and (etiocholanone, androsterone, pregnandiol, pregnantriol, pregnantriolone, 11-keto etiocholanone and 11-OH androsterone) by gas chromatography. Our results show that on termination of the treatment there was a significant rise in the prolactin and DHEA-S serum levels and a drop in the FSH serum levels but not of LH. In addition there was a marked increase in all the androgen levels studied, (etiocholanone, androsterone and 11-keto etiocholanone) with the exception of testosterone.

Stimulatory action of prolactin on gonadotropin secretion in vitro, 1989

"Oestradiol negative feedback inhibition on LH secretion during lactation is prolonged in adolescent primiparous rhesus monkeys. 1993":

With respect to oestradiol negative feedback inhibition of LH, oestradiol treatment effectively suppressed serum LH concentrations at all points during lactation up to week 31, at which time LH concentrations were maximally suppressed in both Prp and Mlt mothers at +6 days after treatment but by day +13 LH values were significantly higher in Mlt females.

Transforming growth factor-beta promotes differentiation of ovarian thecal-interstitial cells but inhibits androgen production. 1989

Treatment with insulin-like growth factor-I (IGF-I) together with LH caused a synergistic increase in androsterone production.

Blood glucose and prolactin in hyperprolactinemic rats exposed to restraint and surgical stress. 1996

Chronic hyperprolactinemia induced a higher (restraint) or longer lasting (surgery) hyperglycemic response in the rat, adding new evidence for a diabetogenic effect of PRL.

Insulin sensitivity and hyperprolactinemia. 2003

It has been shown that prolactin (PRL) induces glucose intolerance, hyperinsulinemia and insulin resistance in several animal species.

Is hyperprolactinemia associated with insulin resistance in non-obese patients with polycystic ovary syndrome?, 2003

Moderate elevations in serum PRL concentration may contribute to insulin resistance in PCOS.


circadian rythms

The role of endocannabinoids in the regulation of luteinizing hormone and prolactin release. Differences between the effects of AEA and 2AG. 2008

Prolactin release

The mechanism of action of cytokines to control the release of hypothalamic and pituitary hormones in infection. 2000

  • IL-1 alpha inhibits growth hormone (GH) release by inhibiting GH-releasing hormone (GHRH) release, which is mediated by NO, and stimulating the somatostatin release, also mediated by NO. IL-1 alpha-induced stimulation of PRL release is also mediated by intrahypothlamic action of NO, which inhibits release of the PRL-inhibiting hormone dopamine.

Role of nitric oxide in the neuroendocrine responses to cytokines. 1998

  • The actions of NO are brought about by its combined activation of guanylate cyclase-liberating cyclic guanosine monophosphate (cGMP) and activation of cyclooxygenase and lipoxygenase with liberation of prostaglandin E2 and leukotrienes, respectively.

Nitric oxide controls the hypothalamic-pituitary response to cytokines. 1997

  • The actions of NO are brought about by its combined activation of guanylate cyclase liberating cyclic guanosine monophosphate and activation of cyclooxygenase and lipoxygenase, with the liberation of prostaglandin E2 and leukotrienes, respectively.

The role of nitric oxide (NO) in control of hypothalamic-pituitary function. 1996

  • The NOS diffuses to the LHRH terminal and activates guanylate cyclase (GC), cyclooxygenase and lipoxygenase causing the release of LHRH via the release of cyclic GMP, PGE2, and leukotrienes, respectively.

Prolactin directly enhances bone turnover by raising osteoblast-expressed receptor activator of nuclear factor kappaB ligand/osteoprotegerin ratio. 2008 fulltext

  • Hyperprolactinemia leads to high bone turnover as a result of enhanced bone formation and resorption. Although its osteopenic effect has long been explained as hyperprolactinemia-induced hypogonadism, identified prolactin (PRL) receptors in osteoblasts suggested a possible direct action of PRL on bone. In the present study, we found that hyperprolactinemia induced by anterior pituitary transplantation (AP), with or without ovariectomy (Ovx), had no detectable effect on bone mineral density and content measured by dual-energy X-ray absorptiometry (DXA). However, histomorphometric studies revealed increases in the osteoblast and osteoclast surfaces in the AP rats, but a decrease in the osteoblast surface in the AP+Ovx rats. The resorptive activity was predominant since bone volume and trabecular number were decreased, and the trabecular separation was increased in both groups. Estrogen supplement (E2) fully reversed the effect of estrogen depletion in the Ovx but not in the AP+Ovx rats. In contrast to the typical Ovx rats, bone formation and resorption became uncoupled in the AP+Ovx rats. Therefore, hyperprolactinemia was likely to have some estrogen-independent and/or direct actions on bone turnover. Osteoblast-expressed PRL receptor transcripts and proteins shown in the present study confirmed our hypothesis. Furthermore, we demonstrated that the osteoblast-like cells, MG-63, directly exposed to PRL exhibited lower expression of alkaline phosphatase and osteocalcin mRNA, and a decrease in alkaline phosphatase activity. The ratios of receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) proteins were increased, indicating an increase in the osteoclastic bone resorption. The present data thus demonstrated that hyperprolactinemia could act directly on bone to stimulate bone turnover, with more influence on bone resorption than formation. PRL enhanced bone resorption in part by increasing RANKL and decreasing OPG expressions by osteoblasts.

Effect of Parathyroid Hormone on Plasma Prolactin in Man 1978

The iv infusion of parathyroid extract or the synthetic fragments of 1–34 bovine or human parathyroid hormone produced a rapid and marked increase of plasma PRL in normal subjects. The stimulation of the release of endogenous parathyroid hormone by administration of disodium EDTA also resulted in a parallel increase of plasma PRL. Parathyroid hormone did not act via plasma cAMP, as the plasma level reached by this nucleotide was too small to produce PRL release. The ingestion of L-dopa 2 h before parathyroid hormone infusion suppressed the PRL response, suggesting that dopamine and parathyroid hormone interact at a common site. As it has been recently shown that PRL stimulates the renal synthesis of 1,25-dihydroxycholecalciferol, the present data suggest that the effect of parathyroid hormone on this synthesis may be due to the increase in plasma PRL.

2014-02-15T09:59:49 - Michela Bolla


Prolactin (PRL) was discovered in 1928 as a pituitary factor that could induce milk secretion in rabbits (Prolactin Signaling in Mammary Gland Development, 1997). However, there were doubts if PRL existed in humans because growth hormone (GH) has PRL-like properties and early attempts to separate PRL and GH had failed. Finally, in 1971, human PRL was isolated (Radioimmunoassay of human prolactin, 1973). This finding opened a new era in the understanding of pituitary diseases and classification of PRL disorders in humans. In the early 1970s the dopamine agonist bromocriptine (Brc) (at that time called CB154) was found to strongly inhibit PRL secretion and lactation in the postpartum period; furthermore, it was understood that it could inhibit PRL and reduce tumour size in prolactinoma patients (Effects of bromocriptine on pituitary tumour size, 1979). These were important discoveries and the beginning of a change in treatment regimen of patients with hyperprolactinemia.

Human PRL is a polypeptide hormone composed of 199 amino acids (23 kDa). The tertiary structure of PRL consists of four-helical bundle topology, stabilized by three disulfide bonds.

Figure 1 - Amino acid sequence of prolactin

Figure 2 - Rendering of the structure of prolactin

The structure is similar to that of two other hormones, GH and placenta lactogen (PL), which all are members of the hematopoietic cytokine family. It is thought that these three hormones evolved from a common ancestral gene by duplication (The tertiary structure and backbone dynamics of human prolactin, 2003). PRL circulates mainly in a monomeric form but there are variants because of posttranslational modifications. In general, these PRL variants have reduced biological activity. Large molecular isoforms (>150 kDa) are termed macroprolactin, which mainly are due to complexes of PRL and IgG. Like other variants, macroprolactin has markedly reduced bioactivity and is considered to exhibit no systemic response in vivo. However, macroprolactin may be identified in different PRL immunoassays and may lead to apparent HPL (Clinical relevance of macroprolactin, 2005).


Human PRL is synthesised in and secreted from lactotroph cells in the anterior pituitary. These cells constitute about 15-25% of functioning anterior pituitary cells. The lactotrophs differ from the other pituitary cells in that they have a high basal secretory activity and PRL secretion is mainly under a tonic inhibition by hypothalamic dopamine (DA). DA reaches
the pituitary via the hypothalamic-pituitary portal system and inhibits PRL by binding to type 2 dopaminergic (D2) receptors on the lactotrophs, leading to a rapid suppression of PRL release from secretory vesicles, inhibition of PRL gene expression and lactotroph proliferation. This mechanism is the rationale for treating patients suffering from hyperprolactinemia with DA agonists. In addition, other potential inhibiting factors on PRL release are somatostatin and γ-aminobutyric acid (GABA). Furthermore, PRL exerts a negative feedback on its own release, by stimulating hypothalamic DA synthesis. Although the control of PRL secretion is mainly inhibitory, there are several known PRL-releasing factors, including thyreotropinreleasing hormone (TRH), vasoactive intestinal polypeptide (VIP), oxytocin, endothelin and estrogens. Moreover, estrogens activate secondary responses that may influence PRL gene transcription. Indeed estrogens inhibit dopaminergic hypothalamic activity and upregulate TRH receptors. Furthermore, PRL secretion is increased by different forms of stressors. A summary of the regulation of PRL secretion is presented in Figure 3. In humans, PRL is secreted episodically during the day with the highest concentrations occurring at sleep (Anterior Pituitary in Textbook of Endocrinology, 2007).

Figure 3 - Regulation of PRL secretion


PRL is best known for its action on the mammary gland during pregnancy. This action includes stimulation of lobuloalveolar growth, milk synthesis and maintenance of milk production. Lately, numerous additional biological functions have been attributed to PRL in humans. These actions have been divided into reproduction, endocrinology and metabolism, growth and development, immunoregulation, brain and behaviour and water and electrolyte balance. A knock-out model of the PRL-receptor (PRLR) gene in mice leads to major reproductive defects with sterility in female mice and an inability to lactate (Prolactin (PRL) and Its Receptor: Actions, Signal Transduction Pathways and Phenotypes Observed in PRL Receptor Knockout Mice, 1998). However, the full diversity of PRL effects in humans is not completely understood. Isolated PRL deficiency has been described in women not able to lactate. Mutations of the PRL gene or PRLR gene has thus far not been described in humans. We therefore do not have a human clinical model to evaluate the consequences of absence of PRL (Isolated prolactin deficiency: a case report, 1992).
PRL acts via a specific membrane receptor that is a single-pass transmembrane protein, a member of the cytokine receptor superfamily and closely related to the GH receptor. The PRLR is activated by ligand-induced dimerisation of two receptor subunits, with signal transduction mainly via the Janus kinase/Stat pathway. Activated Stat proteins
translocate into the nucleus and bind to specific promoter elements on PRL-responsive genes (The prolactin/growth hormone receptor family: structure/function relationships, 1997).

Figure 4 - Ligand induced dimerization and phosphorilation

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