Elevation of Plasma Neurophysin in Women on Oral Contraceptives

Abstract

A B S T R A C T The effect of oral contraceptives on the neurohypophysis was demonstrated by changes in the plasma level of a posterior pituitary protein, neurophysin. Neurophysins are intraneuronal proteins associated with oxytocin and vasopressin. They have been shown to be released into the bloodstream. The resting plasma level of neurophysin in normal nonpregnant women is 0.69 ng/ ml+0.7 SD. In women on oral contraceptives, the plasma level is 6.4 ng/ml+4.2 SD (P < 0.001). Estrogen rather than progesterone causes the elevated neurophysin. The effect is observed within 12-24 h of estrogen administration and disappears 3-11 days after estrogen is discontinued.The results indicate that oral contraceptives act on the neurohypophysis and that estrogen is a potent pharmacologic stimulus useful in studying synthesis and release of neurophysin.

Isolation, assay, and secretion of individual human neurophysins.

“…6 demonstrates the elevation of this neurophysin in five men given 10 mg diethylstilbestrol (DES) for 2 days. This and other data have demonstrated that it is the estrogen of oral contraceptives that causes the neurophysin elevation (19), and we refer to this neurophysin as ESN. No significant difference is measureable using the other NSN neurophysin assay in women on oral contraceptives (2.0±2.0 SD) nor in the DES-treated males (Fig.…”

“…This accounts for the ease of measuring neurophysin in women who are pregnant (9,24) and in women who are taking oral contraceptives (19). The human neurophysin studies described by Legros and Franchimont (9) specifically denied an elevation of neurophysin after cigarette smoking, indicating that this heterologous assay did not detect NSN.…”

Elevation of Oxytocin and the Oxytocin-Associated Neurophysin in the Plasma of Normal Women during Midcycle*

“…The only known pharmacological stimulus for oxytocin secretion and its associated neurophysin in the human is the administration of estrogen (2,4). Both oxytocin and ESN were elevated in the plasma of normal men and women after the ingestion of estrogen, either acutely or chronically (2,5). Oxytocin increased as early as 12 h after the ingestion of a single dose of 100 jug estrogen orally, and the elevation was sustained until 36 h. This elevation in the level of oxytocin was not a natural spontaneous fluctuation of oxytocin because levels of oxytocin in plasma measured serially over 4 h showed no fluctuations in the level of oxytocin in either individuals who were ingesting estrogen or those not receiving the hormone.…”

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

“…E: enhances the electrical activity of magnocellular oxytocin neurons [II, 1 2 ], stimulates oxytocin se cretion into the pituitary portal circulation [13], and releases the oxytocin-associated neurophysin into the peripheral circulation [ 14,15], E: also has effects upon oxytocin neurons that are dis tributed in brain areas other than the classical neurohypophy sial tract. Rhodes et al [35] found that the oxytocinergic neur ons in the PVN of the rat that concentrate E?…”

“…Gonadal steroids, in particular estradiol (E2), are known to have multiple effects upon oxytocin neurons. Administration of E2 enhances the electrical activity of magnocellular oxytocin neurons [11,12], stimulates oxytocin secretion into the pituitary portal circulation [13], releases the oxytocinassociated neurophysin into the peripheral circulation [14,15], and increases oxytocin receptors in the ventromedial nucleus of the hypothalamus [16]. The oxytocin content of the PVN [17], the posterior pituitary [18], and the spinal cord 119, 20] changes across the estrous cycle in the rat.…”