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The influence of gonadal steroids on the release and actions of neurohypophysial hormones
Regulatory Peptides, 45 (1993) 193-196
193
© 1993 Elsevier SciencePublishers B.V. All rights reserved 0167-0115/93/$06.00 REGPEP 01305
The influence of gonadal steroids on the release and actions of neurohypophysial hormones M a r y L. Forsling Department of Gynaecology, UMDS, London (UK) K e y words: Oxytocin; Vasopressin; Oestrogen; Progesterone; Natriuresis; Antidiuresis
Introduction Altered fluid balance has been described over the oestrous and menstrual cycles [1] and during pregnancy [2]. Of the many hormones which could potentially contribute to the observed changes, the neurohypophysial hormone vasopressin (AVP) has been ascribed a role. Oxytocin (OT) has recently been shown to be natriuretic in the rat [3,4] and dog [5] and to be released in response to altered tonicity [6] and volume [7]. This hormone, therefore, could also play a role in the changes seen in the rat and possibly other species. The contribution ofneurohypophysial hormones to the changes in salt and water balance over reproductive cycles has recently been the subject of a number of investigations.
Effect of gonadal steroids on the release of neurohypophysial hormones Although not found by all investigators, initial studies in the human revealed that circulating conCorrespondence to: M.L. Forsling, Department of Gynaecology, UMDS, St. Thomas's Campus, Lambeth Palace Road, London SE1 7EH, UK.
centrations of AVP and OT can vary over the menstrual cycle with a peak at the time of ovulation [ 8,9]. The changes appeared to result from the altering concentrations of gonadal steroids as administration of oestrogen stimulated AVP release while progesterone was inhibitory [ 10]. When studies were performed in rats, it was found that circulating hormone concentrations also depended on the stage of the cycle [11,12], the magnitude of the daily diurnal increase in hormone concentration varying on each of the four days [13 ]. To determine if the observed changes resuited from altered clearance of the hormones, studies have now been performed in the rat in which OT and AVP clearance have been monitored on each day of the oestrous cycle. No significant variation in the plasma clearance of AVP was seen, but that for OT was significantly lower on dioestrus I than oestrus or pro-oestrus, which could contribute to the variations seen [13]. The increased plasma oxytocin concentrations seen during the luteal phase of the cycle in ruminants derive largely from the ovary [ 14], tissue which, however, appears to make no significant contribution to circulating hormone concentrations in either the human or the rat. That the ovary contributes to the control of release from the neurohypophysis is confirmed by the finding that ovariectomy results in a
194 reduction in circulating AVP concentrations and in the normal increase seen over the daylight hours [ 15 ]. Similarly, suppression of the oestrous cycle by the administration of the anti-oestrogen preparation tamoxifen or the long acting L H R H analogue Zoladex results in reduced basal and stimulated AVP secretion [15]. These observations have now been extended to the human. In groups of premenopausal women undergoing hysterectomy and oophorectomy for benign gynaecological conditions, AVP but not OT concentrations were found to be reduced, falling from 0.37+0.03 to 0.26+0.01/~U/ml (P>0.05, n = 19). There was a similar fall in plasma AVP concentrations in Zoladex treated women. In the rat administration of oestrogen and progesterone alone or in combination failed to return the concentrations to normal [16]. Durr etal. [17] also found these steroids were without effect in intact rats, although Skowsky et al. [ 11] reported that oestradiol stimulated AVP release while Crofton et al. [18] found that progesterone was inhibitory in rats ovariectomised while immature. In investigating the contribution of gonadal hormones to the control of neurohypophysial secretion, investigators have also followed the responses to various stimuli of hormone release in the male and in female animals at different stages of the cycle or following oestrogen and progesterone treatment. Gender differences in the control of AVP secretion have been noted. The osmotic threshold for AVP release is lower in females than in males [ 19], and the hormone release in response to haemorrhage greater [20]. Sexual dimorphism has also been reported for O T release [21]. In addition treatment with oestradiol has been found to increase the magnitude of the increase in plasma AVP for a given change in plasma osmolality [22]. Determining direct effects of oestrogen and progesterone on neurohypophysial hormone release is difficult in vivo, because of the complex effects on fluid balance induced. Thus, oestradiol affects ingestive behaviour [23], while both hormones influence salt and water handling by the kidney. Studies have therefore been performed on the modulating effect of
ovarian steroids on hormone release from long term primary cultures of hypothalamic neurones. Results on days 8, 11, 15, 17 and 22 from cultures in a medium with varying concentrations of oestradiol and progesterone, alone and in combination, indicated that oestradiol augments the basal secretion of AVP (Fig. 1) and, in some situations, OT. This effect is most marked in the presence of low concentrations of progesterone. Stimulated hormone release was not significantly influenced by the combinations of steroids employed.
Effect of gonadal steroids on the action of neurohypophysial hormones Although AVP concentrations fell on ovariectomy, there was little change in fluid balance [23]. Similarly, changes in fluid balance are not as marked over the oestrous cycle as might be expected from the changing neurohypophysial hormone concentrations. Therefore, the renal response to AVP, like that of the cardiovascular response [20,24], could be dependent on the stage of the oestrous cycle and be modified by oestrogen. The renal responsiveness to
~, 1.00.8o
"~ 0.6, 0,4'~ 0.2o
>"
0.0
~b
2'o
3'0
Day Fig. 1. Basal release of AVP from hypothalamiccells cultured in a mediumcontaining 10- 11M progesterone([~), 10- 11M oestrogen (m) or 10 xl progesterone with 10 7 M oestrogen (0).
195 short term infusions o f O T a n d AVP, which prod u c e d c o n c e n t r a t i o n s in the physiological range, was m o n i t o r e d on each d a y o f the oestrous cycle. Jugular vein cannulation was p e r f o r m e d u n d e r anaesthesia in female Sprague D a w l e y rats. After at least 24 h for recovery the rats were p l a c e d in m e t a b o l i s m cages a n d infused with 0.077 mol NaC1/1 at 150 # l / m i n for an equilibration period o f n o t less t h a n 3.5 h. T i m e d urine collections were then m a d e for a control period o f at least 45 min, during the a d m i n i s t r a t i o n o f A V P or O T for 60 min and for a final period o f saline infusion o f 90 min. Both the natriuresis and antidiuresis p r o d u c e d by A V P given in a d o s e o f 4 0 / z U / min s h o w e d significant changes over the four days o f the cycle, the r e s p o n s e s being significantly greater on p r o - o e s t r u s than oestrus (Fig. 2). W i t h d o s e s o f 50 a n d 100 # U / m i n oxytocin consistently p r o d u c e d a
diuretic response. H o w e v e r , on dioestrus I d o s e s o f 12.5 and 25 # U / m i n p r o d u c e d an antidiuresis, that with 2 5 / ~ U / m i n being statistically significant. As in the male rat, O T was found to be natriuretic, the smallest change in s o d i u m excretion being o b s e r v e d on dioestrus I. O v a r i e c t o m y o f the rat was found to have differential effects on the anfidiuretic and natriuretic responses to AVP. The antidiuresis o b s e r v e d was o f a similar m a g n i t u d e to that seen on pro-oestrus, but the natriuresis was similar to that seen on oestrus. O e s t r a d i o l treatment with or without progesterone h a d no significant effect on the magnitude o f either the antidiuresis or natriuresis in o v a r i e c t o m i s e d rats. H o w e v e r , progesterone alone a u g m e n t e d the natriuresis while reducing the antidiuresis. O T infused at a rate o f 50 # U / m i n into o v a r i e c t o m i s e d rats prod u c e d a small natriuresis, which increased with steroid treatment, and a small diuresis.
60
Acknowledgement 50
40
Z
~ii!i.ii~ili~i
30 80
References
60 "~
F i n a n c i a l s u p p o r t for these studies from the W e l l c o m e Trust, The Special Trustees for St. Thom a s ' H o s p i t a l a n d the Central R e s e a r c h F u n d o f L o n d o n University is gratefully acknowledged.
40 20 <
P
O
DI
DII
Fig. 2. The magnitude of the anfidiuresis and natriuresis in response to AVP infusion (40 #U/rain) on each day of the oestrous cycle; P, pro-oestrus; O, oestrus; D I, dioestrus I; D II, dioestrus II. Infusions commenced around 14.00 h, except for that shown by the hatched blocks on pro-oestrus, which commenced at 19.00 h.
1 Baylis, P.H., Spruce, B.A. and Burd, J., Osmoregulation of vasopressin secretion during the menstrual cycle. In R.W. Schrier (Ed.), Vasopressin, Raven Press, New York, 1985, pp. 241-248. 2 Olsson, K., Pregnancy - a challenge to water balance, Trends Pharmacol. Sci., 1 (1986) 131-134. 3 Verbalis, J. G., Mangione, M. P. and Stricker, E.M., Oxytocin produces natriuresis in rats at physiological plasma concentrations, Endocrinology, 128 (1991) 1317-1322. 4 Windle, R.J. and Forsling, M. L., The renal actions of oxytocin in the conscious rat, J. Physiol. Pharmacol., 42 (1991) 417-425. 5 Andersen, S.E., Engstrom, T. and Bie, P., Effects on renal sodium and potassium excretion of vasopressin and oxytocin in conscious dogs, Acta Physiol. Scand., 145 (1992) 267-274.
196 6 Brimble, M.J., Dyball, R. E.J. and Forsling, M.L., Oxytocin release following osmotic activation of oxytocin neurones in the rat paraventricular and supraoptic nuclei, J. Physiol., 278 (1978) 69-78. 7 Stricker, E.M. and Verbalis, J. G., Interaction of osmotic and volume stimuli in regulation of neurohypophysial secretions in the rat, Am. J. Physiol., 250 (1986) R267-275. 8 Forsling, M.L., Akerlund, M. and Stromberg, P., Variations in plasma concentrations of vasopressin during the menstrual cycle, J. Endocrinol., 89 (1981) 263-266. 9 Mitchell, M.D., Haynes, P.J., Andereson, A.B.M. and Turnbull, A.C., Plasma oxytocin concentrations during the menstrual cycle, Eur. J. Obstet. Gynec. Reprod. Biol., 12 (1981) 195-200. 10 Forsling, M.L., Stromberg, P. and Akerlund, M., Effect of ovarian steroids on vasopressin release, J. Endocrinol., 95 (1982) 147-151. 11 Skowsky, W. R., Swan, L. and Smith, P., Effect of sex steroids on arginine vasopressin release in intact and castrated male and female rats, Endocrinology, 104 (1979) 105-108. 12 Ho, L.L. and Lee, J.N., Ovarian and circulating concentrations of oxytoein and vasopressin during the oestrous cycle of the rat, Acta Endocrinol., 126 (1992) 530-534. 13 Windle, R.J. and Forsling, M.L., Variations of oxytocin secretion over the four day oestrous cycle of the rat, J. Endocrinol., 136 (1993) 305-311. 14 Wathes, D.C., Oxytocin and vasopressin in the gonads, Oxford Rev. Reprod. Biol., 11 (1989) 226-283. 15 Forsling, M.L., Kelestimur, H. and Windle, R.J., The influence of reproductive status on vasopressin release in the rat, J. Endocrinol., 130 (1991) 387-393. 16 Forsling, M.L. and Peysner, K., Ovarian hormones and va-
17
18
19
20
21
22
23
24
sopressin release in the rat, In Proceedings of the Fourth International Conference on the Neurohypophysis: New Aspects of Function, Morphology and Regulation, Oxford University Press, Oxford, 1990, pp. 172-174. Durr, J.A., Stamoutsos, B. and Lindheimer, M.D., Osmoregulation during pregnancy in the rat. Evidence for resetting of the threshold for vasopressin secretion during gestation, J. Clin. Invest., 68 (1981) 337-346. Crofton, J.T., Baer, P.G., Share, L. and Brooks, D.P., Vasopressin release in male and female rats: effects of gondadectomy and treatment with gonadal steroid hormones, Endocrinology, 117 (1985) 1195-1200. Crofton, J. and Share, L., Osmotic control of vasopressin release in male and female rats, Am. J. Physiol., 257 (1989) R738-743. Crofton, J. T. and Share, L., Sexual dimorphism in vasopressin and cardiovascular responses to haemorrhage in the rat, Circ. Res., 66 (1990) 345-353. Carter, D.A. and Lightman, S.L., Diurnal pattern of stressevoked neurohypophysial hormone secretion: sexual dimorphism in rats, Neurosci. Lett. 71 (1986) 252-255. Barron, W.M., Schreiber, J. and Lindheimer, M.D., Effect of ovarian sex steroids on osmoregulation and vasopressin secretion in the rat, Am. J. Physiol., 250 (1986) E352-E361. Peysner, K. and Forsling, M.L., Effect of ovariectomy and treatment with ovarian steroids on vasopressin release and fluid balance in the rat, J. Endocrinol., 124 (1990) 277-284. St. Louis, J., Parent, A., Lariviere, R. and Schiffrin, E.L., Vasopressin responses and receptors in the mesenteric vasculature of estrogen treated rats, Am. J. Physiol., 251 (1986) H885-H889.
193
© 1993 Elsevier SciencePublishers B.V. All rights reserved 0167-0115/93/$06.00 REGPEP 01305
The influence of gonadal steroids on the release and actions of neurohypophysial hormones M a r y L. Forsling Department of Gynaecology, UMDS, London (UK) K e y words: Oxytocin; Vasopressin; Oestrogen; Progesterone; Natriuresis; Antidiuresis
Introduction Altered fluid balance has been described over the oestrous and menstrual cycles [1] and during pregnancy [2]. Of the many hormones which could potentially contribute to the observed changes, the neurohypophysial hormone vasopressin (AVP) has been ascribed a role. Oxytocin (OT) has recently been shown to be natriuretic in the rat [3,4] and dog [5] and to be released in response to altered tonicity [6] and volume [7]. This hormone, therefore, could also play a role in the changes seen in the rat and possibly other species. The contribution ofneurohypophysial hormones to the changes in salt and water balance over reproductive cycles has recently been the subject of a number of investigations.
Effect of gonadal steroids on the release of neurohypophysial hormones Although not found by all investigators, initial studies in the human revealed that circulating conCorrespondence to: M.L. Forsling, Department of Gynaecology, UMDS, St. Thomas's Campus, Lambeth Palace Road, London SE1 7EH, UK.
centrations of AVP and OT can vary over the menstrual cycle with a peak at the time of ovulation [ 8,9]. The changes appeared to result from the altering concentrations of gonadal steroids as administration of oestrogen stimulated AVP release while progesterone was inhibitory [ 10]. When studies were performed in rats, it was found that circulating hormone concentrations also depended on the stage of the cycle [11,12], the magnitude of the daily diurnal increase in hormone concentration varying on each of the four days [13 ]. To determine if the observed changes resuited from altered clearance of the hormones, studies have now been performed in the rat in which OT and AVP clearance have been monitored on each day of the oestrous cycle. No significant variation in the plasma clearance of AVP was seen, but that for OT was significantly lower on dioestrus I than oestrus or pro-oestrus, which could contribute to the variations seen [13]. The increased plasma oxytocin concentrations seen during the luteal phase of the cycle in ruminants derive largely from the ovary [ 14], tissue which, however, appears to make no significant contribution to circulating hormone concentrations in either the human or the rat. That the ovary contributes to the control of release from the neurohypophysis is confirmed by the finding that ovariectomy results in a
194 reduction in circulating AVP concentrations and in the normal increase seen over the daylight hours [ 15 ]. Similarly, suppression of the oestrous cycle by the administration of the anti-oestrogen preparation tamoxifen or the long acting L H R H analogue Zoladex results in reduced basal and stimulated AVP secretion [15]. These observations have now been extended to the human. In groups of premenopausal women undergoing hysterectomy and oophorectomy for benign gynaecological conditions, AVP but not OT concentrations were found to be reduced, falling from 0.37+0.03 to 0.26+0.01/~U/ml (P>0.05, n = 19). There was a similar fall in plasma AVP concentrations in Zoladex treated women. In the rat administration of oestrogen and progesterone alone or in combination failed to return the concentrations to normal [16]. Durr etal. [17] also found these steroids were without effect in intact rats, although Skowsky et al. [ 11] reported that oestradiol stimulated AVP release while Crofton et al. [18] found that progesterone was inhibitory in rats ovariectomised while immature. In investigating the contribution of gonadal hormones to the control of neurohypophysial secretion, investigators have also followed the responses to various stimuli of hormone release in the male and in female animals at different stages of the cycle or following oestrogen and progesterone treatment. Gender differences in the control of AVP secretion have been noted. The osmotic threshold for AVP release is lower in females than in males [ 19], and the hormone release in response to haemorrhage greater [20]. Sexual dimorphism has also been reported for O T release [21]. In addition treatment with oestradiol has been found to increase the magnitude of the increase in plasma AVP for a given change in plasma osmolality [22]. Determining direct effects of oestrogen and progesterone on neurohypophysial hormone release is difficult in vivo, because of the complex effects on fluid balance induced. Thus, oestradiol affects ingestive behaviour [23], while both hormones influence salt and water handling by the kidney. Studies have therefore been performed on the modulating effect of
ovarian steroids on hormone release from long term primary cultures of hypothalamic neurones. Results on days 8, 11, 15, 17 and 22 from cultures in a medium with varying concentrations of oestradiol and progesterone, alone and in combination, indicated that oestradiol augments the basal secretion of AVP (Fig. 1) and, in some situations, OT. This effect is most marked in the presence of low concentrations of progesterone. Stimulated hormone release was not significantly influenced by the combinations of steroids employed.
Effect of gonadal steroids on the action of neurohypophysial hormones Although AVP concentrations fell on ovariectomy, there was little change in fluid balance [23]. Similarly, changes in fluid balance are not as marked over the oestrous cycle as might be expected from the changing neurohypophysial hormone concentrations. Therefore, the renal response to AVP, like that of the cardiovascular response [20,24], could be dependent on the stage of the oestrous cycle and be modified by oestrogen. The renal responsiveness to
~, 1.00.8o
"~ 0.6, 0,4'~ 0.2o
>"
0.0
~b
2'o
3'0
Day Fig. 1. Basal release of AVP from hypothalamiccells cultured in a mediumcontaining 10- 11M progesterone([~), 10- 11M oestrogen (m) or 10 xl progesterone with 10 7 M oestrogen (0).
195 short term infusions o f O T a n d AVP, which prod u c e d c o n c e n t r a t i o n s in the physiological range, was m o n i t o r e d on each d a y o f the oestrous cycle. Jugular vein cannulation was p e r f o r m e d u n d e r anaesthesia in female Sprague D a w l e y rats. After at least 24 h for recovery the rats were p l a c e d in m e t a b o l i s m cages a n d infused with 0.077 mol NaC1/1 at 150 # l / m i n for an equilibration period o f n o t less t h a n 3.5 h. T i m e d urine collections were then m a d e for a control period o f at least 45 min, during the a d m i n i s t r a t i o n o f A V P or O T for 60 min and for a final period o f saline infusion o f 90 min. Both the natriuresis and antidiuresis p r o d u c e d by A V P given in a d o s e o f 4 0 / z U / min s h o w e d significant changes over the four days o f the cycle, the r e s p o n s e s being significantly greater on p r o - o e s t r u s than oestrus (Fig. 2). W i t h d o s e s o f 50 a n d 100 # U / m i n oxytocin consistently p r o d u c e d a
diuretic response. H o w e v e r , on dioestrus I d o s e s o f 12.5 and 25 # U / m i n p r o d u c e d an antidiuresis, that with 2 5 / ~ U / m i n being statistically significant. As in the male rat, O T was found to be natriuretic, the smallest change in s o d i u m excretion being o b s e r v e d on dioestrus I. O v a r i e c t o m y o f the rat was found to have differential effects on the anfidiuretic and natriuretic responses to AVP. The antidiuresis o b s e r v e d was o f a similar m a g n i t u d e to that seen on pro-oestrus, but the natriuresis was similar to that seen on oestrus. O e s t r a d i o l treatment with or without progesterone h a d no significant effect on the magnitude o f either the antidiuresis or natriuresis in o v a r i e c t o m i s e d rats. H o w e v e r , progesterone alone a u g m e n t e d the natriuresis while reducing the antidiuresis. O T infused at a rate o f 50 # U / m i n into o v a r i e c t o m i s e d rats prod u c e d a small natriuresis, which increased with steroid treatment, and a small diuresis.
60
Acknowledgement 50
40
Z
~ii!i.ii~ili~i
30 80
References
60 "~
F i n a n c i a l s u p p o r t for these studies from the W e l l c o m e Trust, The Special Trustees for St. Thom a s ' H o s p i t a l a n d the Central R e s e a r c h F u n d o f L o n d o n University is gratefully acknowledged.
40 20 <
P
O
DI
DII
Fig. 2. The magnitude of the anfidiuresis and natriuresis in response to AVP infusion (40 #U/rain) on each day of the oestrous cycle; P, pro-oestrus; O, oestrus; D I, dioestrus I; D II, dioestrus II. Infusions commenced around 14.00 h, except for that shown by the hatched blocks on pro-oestrus, which commenced at 19.00 h.
1 Baylis, P.H., Spruce, B.A. and Burd, J., Osmoregulation of vasopressin secretion during the menstrual cycle. In R.W. Schrier (Ed.), Vasopressin, Raven Press, New York, 1985, pp. 241-248. 2 Olsson, K., Pregnancy - a challenge to water balance, Trends Pharmacol. Sci., 1 (1986) 131-134. 3 Verbalis, J. G., Mangione, M. P. and Stricker, E.M., Oxytocin produces natriuresis in rats at physiological plasma concentrations, Endocrinology, 128 (1991) 1317-1322. 4 Windle, R.J. and Forsling, M. L., The renal actions of oxytocin in the conscious rat, J. Physiol. Pharmacol., 42 (1991) 417-425. 5 Andersen, S.E., Engstrom, T. and Bie, P., Effects on renal sodium and potassium excretion of vasopressin and oxytocin in conscious dogs, Acta Physiol. Scand., 145 (1992) 267-274.
196 6 Brimble, M.J., Dyball, R. E.J. and Forsling, M.L., Oxytocin release following osmotic activation of oxytocin neurones in the rat paraventricular and supraoptic nuclei, J. Physiol., 278 (1978) 69-78. 7 Stricker, E.M. and Verbalis, J. G., Interaction of osmotic and volume stimuli in regulation of neurohypophysial secretions in the rat, Am. J. Physiol., 250 (1986) R267-275. 8 Forsling, M.L., Akerlund, M. and Stromberg, P., Variations in plasma concentrations of vasopressin during the menstrual cycle, J. Endocrinol., 89 (1981) 263-266. 9 Mitchell, M.D., Haynes, P.J., Andereson, A.B.M. and Turnbull, A.C., Plasma oxytocin concentrations during the menstrual cycle, Eur. J. Obstet. Gynec. Reprod. Biol., 12 (1981) 195-200. 10 Forsling, M.L., Stromberg, P. and Akerlund, M., Effect of ovarian steroids on vasopressin release, J. Endocrinol., 95 (1982) 147-151. 11 Skowsky, W. R., Swan, L. and Smith, P., Effect of sex steroids on arginine vasopressin release in intact and castrated male and female rats, Endocrinology, 104 (1979) 105-108. 12 Ho, L.L. and Lee, J.N., Ovarian and circulating concentrations of oxytoein and vasopressin during the oestrous cycle of the rat, Acta Endocrinol., 126 (1992) 530-534. 13 Windle, R.J. and Forsling, M.L., Variations of oxytocin secretion over the four day oestrous cycle of the rat, J. Endocrinol., 136 (1993) 305-311. 14 Wathes, D.C., Oxytocin and vasopressin in the gonads, Oxford Rev. Reprod. Biol., 11 (1989) 226-283. 15 Forsling, M.L., Kelestimur, H. and Windle, R.J., The influence of reproductive status on vasopressin release in the rat, J. Endocrinol., 130 (1991) 387-393. 16 Forsling, M.L. and Peysner, K., Ovarian hormones and va-
17
18
19
20
21
22
23
24
sopressin release in the rat, In Proceedings of the Fourth International Conference on the Neurohypophysis: New Aspects of Function, Morphology and Regulation, Oxford University Press, Oxford, 1990, pp. 172-174. Durr, J.A., Stamoutsos, B. and Lindheimer, M.D., Osmoregulation during pregnancy in the rat. Evidence for resetting of the threshold for vasopressin secretion during gestation, J. Clin. Invest., 68 (1981) 337-346. Crofton, J.T., Baer, P.G., Share, L. and Brooks, D.P., Vasopressin release in male and female rats: effects of gondadectomy and treatment with gonadal steroid hormones, Endocrinology, 117 (1985) 1195-1200. Crofton, J. and Share, L., Osmotic control of vasopressin release in male and female rats, Am. J. Physiol., 257 (1989) R738-743. Crofton, J. T. and Share, L., Sexual dimorphism in vasopressin and cardiovascular responses to haemorrhage in the rat, Circ. Res., 66 (1990) 345-353. Carter, D.A. and Lightman, S.L., Diurnal pattern of stressevoked neurohypophysial hormone secretion: sexual dimorphism in rats, Neurosci. Lett. 71 (1986) 252-255. Barron, W.M., Schreiber, J. and Lindheimer, M.D., Effect of ovarian sex steroids on osmoregulation and vasopressin secretion in the rat, Am. J. Physiol., 250 (1986) E352-E361. Peysner, K. and Forsling, M.L., Effect of ovariectomy and treatment with ovarian steroids on vasopressin release and fluid balance in the rat, J. Endocrinol., 124 (1990) 277-284. St. Louis, J., Parent, A., Lariviere, R. and Schiffrin, E.L., Vasopressin responses and receptors in the mesenteric vasculature of estrogen treated rats, Am. J. Physiol., 251 (1986) H885-H889.