Factors influencing sex hormone uptake by rat brain regions. II. Effects of neonatal treatment and hypophysectomy on testosterone uptake.
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Biomedical subjects
Publications and source records attributed to D W Pfaff.
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Radioactivity was found in cell bodies of neurons and glial cells throughout brains of male and female rats that had been injected with either testosterone-H(3) or estradiol-H(3). Uptake by limbic and hypothalamic structures was higher and longer lasting than that in nonlimbic structures. In all brains, the preoptic area, prepiriform cortex, olfactory tubercle, and septum had particularly high, long-lasting uptake of both hormones.
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Bath application of sulfated or non-sulfated cholecystokinin octapeptide (CCK-8s or CCK-8ns, respectively) at concentrations of 25 to 250 nM stimulated the firing activity of 40 to 80% of neurons recorded from the ventromedial nucleus (VMN) in hypothalamic slices maintained in vitro. On the basis of molarity or the percentages of neurons affected, CCK-8s was about 2 to 10 times more potent than CCK-8ns. However, qualitatively, the two forms of CCK-8 were virtually identical: both had a stimulatory action on VMN neurons; both affected VMN neurons in a dose-dependent fashion; both could desensitize their own stimulatory action; and both could cross-desensitize the stimulatory action of the other. These results indicate that not only CCK-8s but also CCK-8ns, which is biologically inactive peripherally, can serve as excitatory neurotransmitters in the VMN, and that both peptides stimulated neurons through the same or a similar neuronal mechanism. It was also found that in the VMN, the stimulatory action of CCK-8 correlated with the actions of norepinephrine, and affected all of the VMN neurons responsive to glucose. Since the actions of glucose and norepinephrine on the activity of VMN neurons are feeding-relevant, our data support the notion that, in addition to acting as a peripheral satiety agent, CCK-8 can also act as a neurotransmitter centrally to mediate satiety.
Ganglia of the nervus terminalis have been shown to contain luteinizing hormone-releasing hormone (LHRH) immunoreactive cells in several mammalian species. These cells are always accompanied by clusters of cells non-immunoreactive to antiserum to LHRH. Using immunocytochemical procedures, we found choline acetyltransferase (ChAT) and vasoactive intestinal polypeptide (VIP) present in cell bodies and in nerve processes throughout the peripheral, intracranial and central projections of the nervus terminalis. In addition, a dense plexus of substance P (SP) immunoreactive fibers was seen in the nasal mucosa surrounding the nasal glandular acini and blood vessels. A number of SP reactive fibers were traced with the olfactory nerves through the cribriform plate of the ethmoid bone and appeared to enter the brain in the area of the central roots of the nervus terminalis.
Certain neuropeptides can facilitate lordosis by acting on midbrain periaqueductal gray (PAG) in estrogen-primed female rats. Here, we investigated responses of individual PAG neurons in vitro, to five neuropeptides: substance P (SP), luteinizing hormone-releasing hormone (LHRH), prolactin (PRL), oxytocin (OT), and thyrotropin-releasing hormone (TRH). Substance P, OT, and TRH excited spontaneous activity of PAG neurons through neurotransmitter-like actions in a dose-dependent manner, whereas LHRH and PRL virtually never affected PAG neurons this way. Oxytocin acted through oxytocin receptors located on the recorded PAG neurons, since excitatory actions of OT were 1) not abolished by synaptic blockade, 2) mimicked by the OT-specific agonist [Thr4, Gly7]OT but not by arginine vasopressin, and 3) blocked by the OT-specific antagonist [d(CH2)5,Tyr(Me)2,Orn8]vasotocin. Although LHRH had no neurotransmitter-like action on spontaneous activity of PAG neurons, it, as well as SP, could modulate responses of some dorsal PAG neurons to GABAA and GABAB agonists or norepinephrine. Neuromodulatory actions of LHRH and SP could help facilitate lordosis through PAG neurons.
Oestrogen, acting in both the brain and pituitary, has a critical role in regulating the reproductive cycle in most mammals. In the brain, oestrogen regulates the release of luteinizing hormone-releasing hormone (LHRH) partly through a mechanism that is blocked by inhibitors of DNA-dependent RNA synthesis or protein synthesis. The distributions of oestrogen-concentrating neurones and of LHRH neurones overlap. The present study was undertaken to determine whether genomic effects of oestrogen mediated by nuclear oestradiol concentration include a direct effect on LHRH-containing neurones. During extensive studies in which the immunocytochemical method for localizing LHRH neurones was optimized and made compatible with the autoradiographic method for detecting oestrogen-concentrating neurones, doubly-labelled cells were very rarely seen. This suggests that genomic regulatory effects of oestrogen which depend on nuclear retention are not exerted directly on most LHRH neurones, but rather must be mediated by another class of neurones.
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