Lactation-inhibiting and prolactin-lowering effect of lisuride and bromocriptine: A comparative study

The prolactin-lowering and lactation-inhibiting effects of lisuride and bromocriptine, two dopaminergic drugs, were compared in a double-blind study. Twenty-six women took lisuride, 0.2 mg b.i.d., and 24 women took bromocriptine, 2.5 mg b.i.d., during 14 days postpartum. Though both drugs gave satisfactory inhibition of puerperal milk production, in these dosages bromocriptine was a more effective lactation inhibitor and prolactin suppressor. After discontinuation of treatment rebound symptoms were more pronounced in the bromocriptine group than in the lisuride group.     

Oxytocin neuron activation in NCAM-deficient mice: anatomical and functional consequences

During stimulated neurosecretion in the rat, oxytocin neurons display a reduced glial coverage and receive an increased number of synapses, changes that are reversed on arrest of stimulation. We identified polysialic acid on the neural cell adhesion molecule (NCAM) as an important mediator of such plasticity. To investigate further the role of this cell surface glycoprotein, we examined the oxytocin system in mice genetically deficient in NCAM. First, ultrastructural analyses revealed that in wild-type mice, the supraoptic nucleus (SON) underwent the same remodelling as in the rat because oxytocin neurons had a diminished astrocytic coverage and increased synaptic input during lactation or chronic salt loading. Surprisingly, the SON displayed this morphology in NCAM-deficient mice as well, whether they were nongestating and hydrated, lactating or dehydrated. The oxytocin system in NCAM-deficient mice was abnormally hyperactive, as illustrated by enhanced plasma and intranuclear concentrations of oxytocin and reduced anxiety-related behaviour. Plasma oxytocin concentrations were also high in lactating NCAM-deficient dams but certain parameters of lactation and maternal behaviour were impaired. NCAM-deficient mice survived ingestion of 2% saline for 7 days and had increased plasma oxytocin but they did not cope with more severe osmotic challenges. Our observations highlight further the remarkable capacity of the adult oxytocin system to undergo neuronal and glial remodelling whenever it is activated. That lack of NCAM did not prevent remodelling indicates that NCAM can be substituted by other molecular mechanisms. Finally, while NCAM deficiency greatly enhanced oxytocin release, it led to impaired oxytocin-dependent physiological and behavioural responses.     

Regulation of galanin-like peptide gene expression by pituitary hormones and their downstream targets

Galanin-like peptide (GALP) mRNA is expressed in neurones of the hypothalamic arcuate nucleus and within pituicytes in the neurohypophysis. Several neuropeptides that are expressed in the arcuate nucleus participate in the neuroendocrine regulation of pituitary hormone secretion. Our objective was to determine the extent to which GALP might be a target for regulation by pituitary hormones or their downstream targets in the rat. The expression of GALP mRNA in the arcuate nucleus was reduced by hypophysectomy as determined by in situ hybridization. However, this did not appear to be attributable to the loss of either gonadal or adrenal steroids because castrated, ovariectomized and adrenalectomized rats had GALP mRNA expression that was indistinguishable from their respective controls. Next, we investigated the effects of growth hormone deficiency on GALP mRNA expression by studying dwarf rats and found that GALP gene expression was not different between dwarf rats and controls. We found that thyroidectomy led to a significant reduction in GALP mRNA expression compared to intact controls, and thyroidectomized rats implanted with thyroxine pellets had GALP mRNA expression that was similar to intact controls. Thus, the reduction of GALP mRNA expression seen in hypophysectomized animals may reflect, in part, a selective loss of thyroid hormone. We also found that the expression of GALP mRNA was increased in the neurohypophysis of lactating rats compared to nonlactating rats, whereas GALP mRNA expression in the arcuate nucleus was unaffected by lactation. This suggests that the induction of GALP gene expression in pituicytes is physiologically associated with activation of oxytocin and vasopressin secretion during lactation.     

Anatomical remodelling of the supraoptic nucleus: changes in synaptic and extrasynaptic transmission

The adult hypothalamic-neurohypophysial system undergoes activity-dependent morphological plasticity that modifies the astrocytic enwrapping of its magnocellular neurones. For a long time, the functional consequences of such changes have remained hypothetical. Modifications in the glial environment of neurones are expected to have important physiological repercussions in view of the various functions played by astrocytes in the central nervous system. In particular, glial cells are essential for uptake of neurotransmitters, including glutamate, and for physically and functionally restricting diffusion of neuroactive substances within the extracellular space. Recent studies performed in the supraoptic nucleus of lactating and chronically dehydrated animals, in conditions where astrocytic coverage of neurones is reduced, have revealed a significant impairment of glutamate clearance. The resulting accumulation of the excitatory amino acid in the extracellular space around glutamatergic inputs causes an enhanced activation of presynaptic metabotropic glutamate receptors that inhibit transmitter release. In the supraoptic nucleus of lactating rats, neuroglial remodelling is accompanied by modification of the geometry, size and diffusion properties of the extracellular space. The latter observations suggest that, in the activated supraoptic nucleus, the range of action and the concentration of released neuroactive substances may be significantly enhanced. Overall, our observations indicate that the glial environment of supraoptic neurones influences synaptic glutamatergic transmission, as well as extrasynaptic forms of communication.     

Magnesium deficiency during lactation as a precipitant of ventricular tachyarrhythmias

A young ICD recipient with a history of syncope and idiopathic polymorphic ventricular tachycardia/ventricular fibrillation presented after an ICD discharge. She had delivered her first child 8 days prior to the event and she had been lactating. Numerous short runs of polymorphic ventricular tachycardia/ventricular fibrillation resolved with aggressive replacement of magnesium and elimination of breast-feeding.     

Changes in the mannan binding lectin (MBL) concentration in human milk during lactation

The mannan binding lectin (MBL) activates the complement system by the lectin pathway after the recognition of some structural motifs (saccharides) present on the surface of microorganisms. MBL has been mostly identified and quantified in human serum by ELISA or microparticle immunonephelometry assays. This article reports the MBL levels as assessed by a microparticle immunonephelometric assay in 76 human milk samples. Immunonephelometry was performed using skim-milk samples diluted 20 times over a calibration range of 0.07-4.82 mg/L. MBL is indeed present in human milk and its concentration decreases significantly during development from colostrum (0.55+/-0.09 mg/L) to transitional (0.18+/-0.02 mg/L) and mature milk (0.17+/-0.02 mg/L). This innate molecule may be involved in the primary defenses of the mammary gland and the neonate, whose immune system is immature. The high levels observed during the first days of lactation support the hypothesis that this molecule plays a key role in limiting the colonization of the newborn gut by pathogens.     

Effect of lifetime lactation on breast cancer risk: a Korean women's cohort study

The objective of our study was to examine the effect of lifetime lactation on breast cancer risk among premenopausal women. The data were from a prospective cohort study with a follow-up period of 6 years in Korea (1995-2000). The cohort was composed of 110,604 premenopausal parous Korean women, aged 20 years and older, who received health insurance from the Korea Medical Insurance Corporation and who had medical evaluations in 1992 and 1994. Multivariate Cox proportional hazard models were tested, controlling for age, age at menarche, number of children, age at first pregnancy, oral contraceptive use, smoking, exercise and obesity. At baseline, 57,440 (51.9%) reported breastfeeding and 4,584 (4.1%) reported breastfeeding more than 24 months. From 1995-2000, 360 incident cases of breast cancer (61.8/100,000 person-years) occurred. Compared to parous women who had no history of lactation, a period of lactation of 13-24 months decreased the risk of breast cancer (RR, 0.7; 95% CI, 0.5-1.1), and this risk was decreased even further for those who breastfed for more than 24 months (RR, 0.6; 95% CI, 0.3-1.0). There was a clear trend of decreasing breast cancer risk with the duration of lactation (p for trend <0.001). In conclusion, our study of a large Korean cohort provides additional empirical evidence to current theoretical conjecture that lactation decreases the risk of breast cancer among premenopausal women.     

HUMAN COLOSTRAL AND BREAST MILK CELLS A Light and Electron Microscopic Study

Abstract. Colostrum and breast milk samples were obtained from 74 women, 18 of whom gave sequential samples. The mean total leukocyte count in colostrum was 3190 cells/mm³. Proportions of macrophages, polymorphs and lymphocytes varied widely; macrophages usually predominated. Serial sampling showed (1) a small fall in total counts through delivery, (2) a fall in total counts and the proportion of PMNs at the onset of lactation, (3) after 1 to 2 weeks of lactation the appearance of cytoplasmic fragments together with epithelial cells which later constituted the main cell type. It was estimated that the total number of leukocytes available to the neonate remained approximately constant during the first 2 weeks of lactation and fell thereafter. Functionally, morphologically and histochemically macrophages in colostrum and breast milk resembled macrophages elsewhere. Their ultrastructure was characterised by filiform surface projections, numerous endocytic vacuoles and lipid droplets in the cytoplasm.