Effect of Estradiol and Progesterone Administration upon the Circadian Rhythm of Oxytocin in the Cerebrospinal Fluid of Rhesus Monkeys

Abstract

The effect of administration of estradiol (E₂) alone or combined with progesterone upon the circadian rhythm of oxytocin concentrations in cerebrospinal fluid (CSF) was examined in adult ovariectomized rhesus monkeys bearing temporary subarachnoid catheters and maintained in a constant photoperiod (lights on 06.00–18.00 h). Animals were subcutaneously implanted with silastic capsules containing 17β-E₂ for 6 days and progesterone for the last 3 days of E₂ administration. Hourly samples of CSF were collected before, during and after gonadal steroid administration and measured for oxytocin by RIA and reverse-phase high-performance liquid chromatography (RP-HPLC). A significant increase in the serum concentration of E₂ and the plasma concentration of oxytocin neurophysin, but not the plasma concentration of oxytocin, was found during gonadal steroid administration. Each animal displayed a dirunal pattern of secretion of oxytocin in CSF with peak and trough levels during light and dark hours, respectively. No significant differences were found across experimental conditions in the following CSF oxytocin parameters: mean level of oxytocin in CSF during the light, dark, or light and dark hours combined; the daily phase or amplitude of the CSF oxytocin rhythm; the peak or nadir concentration of oxytocin in CSF; or the total amount of oxytocin secreted into the CSF as expressed as the area under the curve (multivariate repeated measures ANOVA). The CSF oxytocin parameters in the animals that were restudied using empty silastic implants were not significantly different across time (multivariate repeated measures ANOVA). Oxytocin immunoreactivity in extracts of CSF collected from 1 monkey before and during gonadal steroid administration eluted from an RP-HPLC column as a single peak in the position of synthetic oxytocin. We conclude that the circadian pattern of oxytocin concentrations in the CSF of monkeys is not significantly altered by administration of estradiol or progesterone.

Effect of Naloxone Administration upon the Diurnal Concentrations of Oxytocin in the Cerebrospinal Fluid of Rhesus and Cynomolgus Monkeys

“…How ever, we have previously reported that ovarian steroid hormones (es tradiol. progesterone) are without effect upon CSF oxytocin concen trations [6], Animals were maintained in a 12 h light: 12 h dark cycle (light. 07.00-19.00 h).…”

“…10 mg/kg i.m., and anesthetized with pentobarbital, 15 mg/kg i.v. Cathe ters were inserted into the femoral vein 2-4 weeks prior to study and kept patent with sterile heparinized (2.5 IU/ml) 0.9% saline ( « 100 ml/day) as previously described [5][6][7], Subarachnoid catheters were inserted aseptically using a standard lumbar puncture technique [5][6][7], The distal tip of the subarachnoid catheter terminated at the first lumbar, last thoracic vertebrae. Animals were placed in a protective jacket that protected the venous and subarachnoid catheters, and a tether (flexible metal cable) wasattached to the jacket.…”

“…Animals were placed in a protective jacket that protected the venous and subarachnoid catheters, and a tether (flexible metal cable) wasattached to the jacket. The tether and catheters connected to a swivel at the top of the cage [5][6][7]. Catheters ran from the top of the swivel through a hole in the wall behind the cage to allow for infusion and withdrawal of the samples from a remote site in an adjacent room [5][6][7].…”

“…Whereas the oxytocin cell bodies of the SON are magnocellular and project to the posterior pitu itary gland, oxytocin cell bodies of the PVN are both mag nocellular and parvocellular, with magnocellular compo nents projecting to the posterior pituitary and parvocellu lar components projecting to central nervous system (CNS) areas other than the posterior pituitary [1][2][3][4], Magnocellular oxytocin neurons that project to the posterior pituitary give rise to oxytocin in the peripheral blood, and parvocellular oxytocin neurons that project to extrahypothalamic brain areas likely give rise to oxytocin within cerebrospinal fluid (CSF) [1][2][3][4], We have previously re ported a method to study CSF oxytocin concentrations in the spinal subarachnoid space of freely moving monkeys [5][6][7], A diurnal variation of oxytocin concentrations is present in CSF collected from lumbar, thoracic and cervi cal subarachnoid spaces but displays a caudal-rostral gra dient in the magnitude of the rhythm, with a greater mag nitude in CSF collected from the lumbar region [5], The elevated concentrations of oxytocin in lumbar CSF likely reflect oxytocin derived from oxytocin nerve terminals in the lumbar spinal cord whose origins are in cell bodies of the dorsal parvocellular portion of the PVN [ I -7],…”

“…We have previously reported a functional separation in the activity of oxytocinergic neurons that give rise to oxy tocin concentrations in the plasma and the lumbar CSF of nonhuman primates [5][6][7], Suckling, a physiological stim ulus that increases oxytocin concentrations in the plasma of monkeys nursing their young, was without effect upon oxytocin concentrations in samples of CSF drawn simul taneously from the lumbar subarachnoid space of lactating animals [7], Similarly, administration of estradiol to rhesus monkeys increased the concentrations of the oxy tocin-associated neurophysin in plasma but not of oxyto cin or its neurophysin in lumbar subarachnoid CSF [6], Moreover, the prominent diurnal variation in concentra tions of oxytocin in CSF samples is not present in plasma samples drawn simultaneously [8,9], Two recent reports in nonprimate species suggest that endogenous opioid pathways may influence the CSF con centrations of oxytocin in nonprimate species [10,11], Kendrick and Keverne [10] have reported that intracerebroventricular administration of the mu opioid receptor antagonist naltrexone to conscious ewes increased the basal concentrations of oxytocin in CSF. Pretreatment of ewes with naltrexone prior to vaginal cervical stimula tion, a stimulus that is reported to increase both peripheal and CSF concentrations of oxytocin in ewes, prevented the increase in CSF oxytocin seen in response to this stim ulus [10].…”