Surgical Treatment of Cystic Pituitary Prolactin-Secreting Macroadenomas: A Single Center Study of 42 Patients.

This study evaluated the therapeutic effects of surgical treatment of cystic pituitary prolactin-secreting macroadenomas. The clinical data of 42 patients with cystic pituitary prolactin-secreting macroadenomas were retrospectively analyzed. Patients were divided into medication plus surgery and surgery alone groups based on the regularity of bromocriptine treatment before surgery. Both groups underwent extra-pseudocapsular transsphenoidal surgery for tumor resection, and postoperative images and clinical follow-up were retrospectively reviewed. We also evaluated patients who opted for long-term treatment with bromocriptine. In the medication plus surgery group, the long-term surgical cure rate and comprehensive remission rate were 33.3% and 41.7%, while in the surgery alone group they were 69.2% and 80.8%, respectively. No severe or permanent complications occurred, and the surgical complication morbidity rate was 10.5%. The rate of tumor progression during the long-term follow-up was 33.3% and 7.7% in the medication plus surgery and surgery alone groups, respectively. The time required for prolactin levels to return to normal in the surgery alone group was significantly faster and the proportion that returned to normal was significantly higher. Direct surgical treatment after diagnosis combined with postoperative individualized bromocriptine adjuvant therapy had better efficacy in patients with cystic pituitary prolactin-secreting macroadenomas, but its long-term effectiveness requires further follow-up.

Prolactin and prolactin receptor expression in the HPG axis and crop during parental care in both sexes of a biparental bird (Columba livia).

During breeding, multiple circulating hormones, including prolactin, facilitate reproductive transitions in species that exhibit parental care. Prolactin underlies parental behaviors and related physiological changes across many vertebrates, including birds and mammals. While circulating prolactin levels often fluctuate across breeding, less is known about how relevant target tissues vary in their prolactin responsiveness via prolactin receptor (PRLR) expression. Recent studies have also investigated prolactin (PRL) gene expression outside of the pituitary (i.e., extra-pituitary PRL), but how PRL gene expression varies during parental care in non-pituitary tissue (e.g., hypothalamus, gonads) remains largely unknown. Further, it is unclear if and how tissue-specific PRL and PRLR vary between the sexes during biparental care. To address this, we measured PRL and PRLR gene expression in tissues relevant to parental care, the endocrine reproductive hypothalamic-pituitary- gonadal (HPG) axis and the crop (a tissue with a similar function as the mammalian mammary gland), across various reproductive stages in both sexes of a biparental bird, the rock dove (Columba livia). We also assessed how these genes responded to changes in offspring presence by adding chicks mid-incubation, simulating an early hatch when prolactin levels were still moderately low. We found that pituitary PRL expression showed similar increases as plasma prolactin levels, and detected extra-pituitary PRL in the hypothalamus, gonads and crop. Hypothalamic and gonadal PRLR expression also changed as birds began incubation. Crop PRLR expression correlated with plasma prolactin, peaking when chicks hatched. In response to replacing eggs with a novel chick mid-incubation, hypothalamic and gonadal PRL and PRLR gene expression differed significantly compared to mid-incubation controls, even when plasma prolactin levels did not differ. We also found sex differences in PRL and PRLR that suggest gene expression may allow males to compensate for lower levels in prolactin by upregulating PRLR in all tissues. Overall, this study advances our understanding of how tissue-specific changes in responsiveness to parental hormones may differ across key reproductive transitions, in response to offspring cues, and between the sexes.

Is idiopathic mild hyperprolactinemia a cardiovascular risk factor?

BACKGROUND: There is a strong relationship between arterial stiffness and endothelial dysfunction and hypertension. How arterial stiffness is affected in elevated PRL conditions is uncertain. Biological action of prolactin contributing to the atherosclerotic process is a new research area. AIMS: We aimed at investigating cardiovascular risk predictability by conducting arterial stiffness measurement in patients with idiopathic hyperprolactinemia. SUBJECTS AND METHODS: The biochemical parameters and arterial stiffness analyses of 54 patients with idiopathic hyperprolactinemia, who had applied to our polyclinic in 2017 and 2018, and 55 healthy volunteers having similar characteristics with regard to age, sex and body mass index. RESULTS: The median prolactin level of the idiopathic hyperprolactinemia patients with a median age of 31 was found to be 45 ng/mL. The peripheral and central blood pressures and pulse wave velocities (PWV) of both the patient group and the control group were found to be similar. Any relations between prolactin levels and blood pressure and arterial stiffness could not be found. DISCUSSION: Our study showed that arterial stiffness did not increase in young patients with idiopathic mild hyperprolactinemia. However, the long-term effects of mildly elevated prolactin levels are unknown. Prospective randomized studies are required, that could reveal more clearly the prolactin-cardiovascular risk relation, and the clinical effects of extra-pituitary hyperprolactinemia.

Prolactin function and putative expression in the brain.

INTRODUCTION: Prolactin is a peptide hormone mainly synthetized and secreted by the anterior pituitary gland, but also by extrapituitary tissues, such as mammary gland, decidua, prostate, skin, and possibly the brain. Similarly, prolactin receptor is expressed in the pituitary gland, many peripheral tissues, and in contrast to prolactin, its receptor has been consistently detected in several brain regions, such as cerebral cortex, olfactory bulb, hypothalamus, hippocampus, amygdala, among others. Classically, prolactin function has been related to the stimulation of lactogenesis and galactopoiesis, however, it is well known that prolactin induces a wide range of functions in different brain areas. PURPOSE: The aim of this review is to summarize recent reports on prolactin and prolactin receptor synthesis and localization, as well as recapitulate both the classic functions attributed to this hormone in the brain and the recently described functions such as neurogenesis, neurodevelopment, sleep, learning and memory, and neuroprotection. CONCLUSION: The distribution and putative expression of prolactin and its receptors in several neuronal tissues suggests that this hormone has pleiotropic functions in the brain.

A combined opiate agonist and antagonist treatment reduces prolactin secreting pituitary tumor growth.

Prolactin secreting pituitary adenomas (prolactinomas) is the most common pituitary tumors in humans. Animal studies have identified aggressive prolactinoma development in fetal alcohol exposed rats. We have recently identified a combination treatment of a µ opioid receptor antagonist naltrexone and a δ opioid receptor agonist D-Ala2-,N-Me-Phe4,Gly-ol Enkephalin (DPDPE) increases innate immune function. In this study, we tested whether naltrexone and DPDPE combination therapy is useful to control pituitary tumor growth. Fetal alcohol exposed and control Fischer 344 female rats at 60 days of age were ovariectomized and received an estrogen implant to induce prolactinomas. Six weeks after the estrogen implant, these animals received treatments of naltrexone and DPDPE or saline. The growth of the pituitary tumor prior to and after opioidergic agent treatments was visualized using magnetic resonance imaging (MRI). At the end of the treatment, pituitary weights, plasma prolactin and splenic levels of cytotoxic factors were determined. Both imaging data and weight data indicated that the volume and the weight of the pituitary were increased more after estrogen treatment in animals exposed to fetal alcohol than control. Naltrexone and DPDPE treatment reduced the weight and volume of the pituitary gland and plasma levels of prolactin in both fetal alcohol exposed and control-fed animals. The treatment of opioidergic agents also increased the levels of cytotoxic factors in the spleen. These data provide a novel possibility in treating pituitary tumors using a combination therapy of naltrexone and DPDPE.

Pregnenolone sulfate regulates prolactin production in the rat pituitary.

Pregnenolone sulfate (PS) is a neuroactive steroid hormone produced in the brain. In this study, the effects of PS on synthesis and secretion of rat pituitary prolactin (PRL) were examined. To accomplish this, GH3 rat pituitary adenoma cells were treated with PS, which showed significantly increased mRNA and protein levels of PRL compared with the control. The mechanism of action responsible for the effects of PS on PRL synthesis and secretion was investigated by pretreating cells with inhibitors of traditional PRL- or the PS-related signaling pathway. PS-stimulated PRL transcription was significantly reduced by inhibitors of PKA, PKC and MAPK, but unchanged by GABAAR and NMDAR inhibitors. Western blotting analysis revealed that the total ERK1/2 level was upregulated in a time-dependent manner following PS treatment. An approximate 10% increase in GH3 cell proliferation was also observed in response to PS relative to the control. In the animal study, levels of PRL in the pituitary and in serum were elevated by PS. PS-stimulated PRL synthesis was also found to be associated with decreased expression of PRL target genes such as GNRH1, FSHB and LHB. These findings show that PS upregulates PRL synthesis and secretion in vivo and in vitro via MAPK signaling, suggesting that it has the potential for use as a therapeutic hormone to treat PRL-related disorders such as hypoprolactinemia and low milk supply.

Use of micro-positron emission tomography with (18)F-fallypride to measure the levels of dopamine receptor-D2 and (18)F-FDG as molecular imaging tracer in the pituitary glands and prolactinomas of Fischer-344 rats.

Dopamine receptor-D2 (DRD2) is the most important drug target in prolactinoma. The aim of this current study was to investigate the role of using micro-positron emission tomography (micro-PET) with (18)F-fallypride and (18)F-fluorodeoxyglucose ((18)F-FDG) as molecular imaging tracer in the pituitary glands and prolactinomas of Fischer-344 (F344) rats and detect the difference of the levels of DRD2 in the pituitary glands and prolactinomas of F344 rat prolactinoma models. Female F344 rat prolactinoma models were established by subcutaneous administration of 15 mg 17ß-estradiol for 8 weeks. The growth of tumors was monitored by the small-animal magnetic resonance imaging and micro-PET. A series of molecular biological experiments were also performed 4 and 6 weeks after pump implantation. The micro-PET molecular imaging with (18)F-fallypride revealed a decreased expression of DRD2 in F344 rat prolactinoma models, but the micro-PET molecular imaging with (18)F-FDG presented an increased uptake in the prolactinoma compared with the pituitary gland. A decreasing trend of levels of DRD2 in F344 rat prolactinoma models was also detected by molecular biological experiments. From this, we can conclude that micro-PET with (18)F-fallypride and (18)F-FDG can be used to assess tumorigenesis of the prolactinomas in vivo and molecular imaging detection of DRD2 level in prolactinoma may be an indication of treatment effect in the animal experiment.