Evidence for the Differential Secretion of Oxytocin and Vasopressin in Man*

Abstract

In the present study we have attempted to answer the question whether vasopressin and oxytocin are secreted together or independently. This subject has been a matter of controversy during the past 35 years. The great variety of methods used in measuring oxytocin and vasopressin activities, the variety of animal species studied, and the variety and magnitude of stimuli employed in different studies make it very difficult to compare results and to draw conclusions as to whether or not there may be independent release of these two neurohypophyseal hormones (1-5).The studies to be described in the present report have been performed in conscious women in whom several relatively mild stimuli known to act on the neurohypophysis were applied under carefully controlled conditions. In the absence of adequate methods for assaying oxytocin and vasopressin directly in plasma, both hormones were assayed by indirect methods that have gained general acceptance. The results strongly suggest that under appropriate conditions oxytocin and vasopressin are released independently of each other by the human neurohypophysis. MethodsStudies in 29 women were carried out during the last weeks of pregnancy (36 to 40 weeks) or during the first week of puerperium, or both.In preparation for the measurement of vasopressin activity, a constant degree of overhydration was induced by the oral administration of 10 to 20 ml of water per kg of body weight or the intravenous administration of a similar amount as 5% glucose in water. Urine was collected through an indwelling catheter every 15 min-* Submitted for publication January 27, 1964; accepted August 10, 1964. Presented at the Forty-fifth Annual Meeting of the Endocrine Society, Atlantic City, N. J., June 13, 1963. Supported by grant 59028 from the Rockefeller Foundation.utes. Venous blood was collected for use in the determination of free water clearance (CH20), solute clearance (Cosm), and creatinine clearance (Ccr). Osmolality was monitored by the freezing point depression method (Fiske osmometer), and creatinine was measured by the method of Bonsnes and Taussky (6). An increase in urine osmolality (decrease in CH20) without significant changes in CCr and Cos.1 was taken as evidence of vasopressin activity (antidiuretic response) (7).In late pregnancy, oxytocic activity was assayed by monitoring intrauterine pressure by the method of Caldeyro-Barcia and associates (8, 9). A thin polyethylene catheter was inserted into the uterine cavity through the anterior abdominal wall and connected to a pressure transducer and a Sanborn Poly-Viso recorder. This procedure has, with long experience, proved to be innocuous. Uterine or "oxytocic" activity was expressed in Montevideo units, representing the product of the amplitude of the contractions in millimeters of mercury multiplied by the frequency of the contractions during a given period (8, 9). During the puerperium, oxytocin was assayed by the measurement of intramammary pressure or "milk-ejecting pressure" by the method of Sica-Blanco and co...

Blood levels of oxytocin and vasopressin during suckling in the rabbit and the problem of their independent release

“…Peeters & Debackere (1963) reported that in well hydrated goats with normal milk yields, diuresis was inhibited only occasionally during milking. Gaitan, Cobo & Mizrachi (1964) did not observe inhibition of diuresis during suckling in twenty-four experiments on lactating women and advanced this result as an argument in favour of independent release of oxytocin and vasopressin. The most direct method of determining whether there is a simultaneous release when milk ejection occurs, is to assay both hormones in samples of blood collected during suckling.…”

The Effect of Hemorrhage and Hypertonic Saline upon Plasma Oxytocin and Arginine Vasopressin in Conscious Dogs*

“…The view that hyperosmolality is a specific stimulus for arginine vasopressin (AVP) release has been challenged by studies showing increases in uterine or milkejecting activity in animals given intracarotid infusions of hypertonic saline (1)(2)(3). However, careful studies in man of the milk-ejecting or uterine responses to iv infusions of hypertonic saline have yielded conflicting results, possibly related in part to the lesser intensity of the osmotic stimulus (4)(5)(6)(7). A major shortcoming of such studies is that AVP possesses substantial intrinsic activity in either milk ejection or uterotonic assays making it difficult to determine with certainty whether or not oxytocin (OT) was actually released (8).…”

Immunochemical Studies on the Storage and Axonal Transport of Neurophysins in the Hypothalamo‐neurohypophyseal System

“…In accord with the separate neurone hypothesis it was found that stimulation of localized areas of the hypothalamus with implanted electrodes could effect an independent release of vasopressin and o~y t o c i n .~*~~* '~~~~ Selective release of vasopressin has also been achieved by carotid occlusion19 and by hemorrhage.11*M*77 Oxytocin is released selectively during p a r t u r i t i~n~~ and by suck-ing14 and in lactating women under osmotic stress. 29 By application of biochemical subcellular fractionation methods t o bovinez0>M*6s and rabbit9 posterior pituitary homogenates, it was shown that a partial separation of oxytocin-and vasopressincontaining vesicles could be obtained on sucrose density gradients. These techniques were also used to obtain pinched-off nerve ending fractions ("neurosecretosomes") with different v a s e pressin/oxytocin ratios,13 and to obtain neurosecretory vesicle fractions from the ox, one of which showed a relative enrichment in oxytocin and neurophysin I and another in vasopressin and neurophysin ILmn Taken together, these biochemical, physiological, and morphological studies suggested that the two hormones were probably stored in separate neurones in HNS together with their respective neurophysins.…”