, the reduction of inhibitory tone during REM permits what can be called ‘excitatory tone’ to be expressed as erection. NPT is clearly impaired in hypogonadal men, and restored to normal with testosterone replacement. The l.c. has testosterone receptors
SANDRA M. EGAN and A. LIVINGSTON
In the presence of 62 μu. or more of [3H]oxytocin/ml there was specific uptake of oxytocin by lactating rat mammary glands in vitro within 400 s under conditions similar to those used in the biossay of oxytocin with rat mammary strips in vitro. This uptake was blocked by pre-incubation with non-radioactive oxytocin. A similar, rapid, specific uptake of oxytocin by uterine tissue in vitro was observed. There was no specific uptake of oxytocin by non-target tissues such as heart and skeletal muscle. Measurements of inulin and water spaces of the tissues showed that, over these short periods of time, diffusion into mammary tissue was much less than into the other tissues. The ratios of uptake of [3H]oxytocin: [3H]inulin and [3H]oxytocin: [3H]water were much higher for mammary tissue than those for other tissues used, indicating a preferential (tissue-specific) uptake. Uterine tissue from stilboestrol-primed rats also showed a preferential uptake of oxytocin, though not as great as that for mammary tissue. It is suggested that the specific uptake of oxytocin by mammary and uterine tissue is due to binding to specific receptors.
There was a variation in the specific uptake of oxytocin with the day of lactation of the mammary tissue, and specific uptake was only observed after the 8th day. This could indicate synthesis of receptors during lactation. In a similar way, synthesis of receptors may occur in the non-pregnant uterus due to the influence of exogenous oestrogens, leading to the increase in specific uptake by non-pregnant uterine tissue for oestrogen-primed rats. There is some evidence of more than one type of binding site for oxytocin. Biological action may only be associated with one of these sites.
J. B. WAKERLEY, R. E. J. DYBALL and D. W. LINCOLN
Recordings of intramammary pressure have been used in recent experiments to demonstrate the intermittent pattern of milk ejection (ME) in the rat (Wakerley & Lincoln, 1971; Lincoln, Hill & Wakerley, 1973). This technique provides 'on-line' but indirect evidence of oxytocin release. Other naturally occurring substances (bradykinin, 5-hydroxytryptamine, acetylcholine and vasopressin) can initiate contractions of the mammary gland and thus mimic the effect of oxytocin (Bisset, Clark, Haldar, Harris, Lewis & Rocha e Silva, 1967). The following experiments were designed to identify oxytocin as the active milk-ejecting principle released during suckling.
Bisset, Clark & Haldar (1970) described an in-vivo method of identifying oxytocin using an antagonist, N-carbamyl-O-methyl-oxytocin, which acts as a competitor for oxytocin receptors. The effects of this antagonist on the contractions of the mammary gland during natural ME were examined. Lactating rats were anaesthetized with tribromoethanol (Lincoln et al. 1973) and two mammary glands in the
S Mukaddam-Daher, M Jankowski, D Wang, A Menaouar and J Gutkowska
We have recently uncovered the presence of an oxytocin system in the heart and found that oxytocin is a physiological regulator of atrial natriuretic peptide (ANP), a diuretic, natriuretic and vasodilator cardiac hormone. However, dynamic changes in these systems during gestation, when mechanisms of volume and pressure homeostasis are altered, are not clear. Accordingly, ANP, oxytocin and oxytocin receptors were evaluated in rat hearts and plasma at three stages of gestation (7, 14 and 21 days) and at 2 and 5 days postpartum. Compared with non-pregnant controls, plasma ANP was elevated in mid-gestation, but significantly decreased at term (21 days), to increase again postpartum. Right and left atrial ANP mRNA levels were not altered throughout gestation but increased by 1.5- to 2-fold postpartum (P<0.01). At term, ANP content in right (8.7+/-1.2 vs 12.7+/-1.1 micro g/mg protein, P<0.04) and left (3.5+/-0.6 vs 8.5+/-2.0 micro g/mg protein, P<0.01) atria increased. These findings imply that decreased plasma ANP at term results from inhibition of release rather than decreased synthesis. In parallel, oxytocin, a stimulator of ANP release, decreased in left atria at day 7 to 50% of non-pregnant levels and remained low throughout gestation. Oxytocin receptor mRNA increased in left atria at 7 and 14 days of gestation by 2- and 5-fold respectively, but decreased at 21 days to lower than non-pregnant levels to increase again (3-fold) postpartum. The changes in oxytocin receptor expression at term and postpartum paralleled oxytocin receptor protein determined by Western blot. These results imply that pregnancy is associated with dynamic changes in the cardiac oxytocin system (peptide and/or receptors), which may influence natriuretic peptide release. Together, these peptides would act on their receptors in the heart, vasculature and kidneys to maintain vascular tone and renal function throughout gestation and postpartum.
G. J. Boer and J. Kruisbrink
A controlled-delivery module based on microporous Accurel polypropylene tubing, implanted subcutaneously in the rat, was used to release oxytocin for at least 40 days both in vitro and in vivo. Using a dosage rate of approximately 650 ng oxytocin per day and implanting the device in rats on day 17 of pregnancy, the known physiological action of oxytocin in advancing labour was confirmed. The increased concentrations of oxytocin in the mothers gave rise to adverse effects; the course of labour was protracted during expulsions of the first pups and the birth weight was reduced. Postnatally, body development of the pups was also affected, although there was partial recovery when the pups started to feed independently. Both pre- and postnatal exposure of pups to an oxytocin-treated mother reduced their body water turnover measured at 1 month of age.
The effects on the course of parturition and during lactation might be explained by a blockade of uterine and mammary gland oxytocin receptors respectively, thereby inhibiting a proper response to pulsatile endogenous oxytocin secretion. The changes in water metabolism, which are opposite to those described for the heterologous hormone vasopressin, are less easy to explain since maternal oxytocin is not supposed to pass the placenta. The results may indicate that clinical use of oxytocin for induction of labour and lactation may have hitherto unrecognized side-effects.
J. Endocr. (1984) 101, 121–129
Eriko Furube, Tetsuya Mannari, Shoko Morita, Kazunori Nishikawa, Ayaka Yoshida, Masanobu Itoh and Seiji Miyata
arginine vasopressin (AVP) and oxytocin (OXT) into the blood circulation from their axonal terminals ( Miyata & Hatton 2002 ). Similarly, they release a variety of neuropeptides into the blood circulation at the median eminence (ME) to control secretion of
G. Robinson and J. J. Evans
We previously demonstrated that oxytocin stimulates LH release from rat pituitary cells in vitro and advances follicular development and ovulation in mice in vivo. This study reports an investigation of rat LH levels following in-vivo administration of oxytocin. Injection of oxytocin (10 mIU/g, i.p.) to rats at 07.00, 08.00 and 09.00 h of pro-oestrus or at 09.00, 10.00 and 11.00 h of pro-oestrus advanced the onset of the LH surge (P<0.005) and attainment of peak concentrations of LH (P<0.02) in peripheral blood. On the other hand, the descending phase of the LH surge and the surge amplitude were not altered by oxytocin. Treatment at 05.00, 06.00 and 07.00 h of pro-oestrus or at 11.00, 12.00 and 13.00 h of pro-oestrus had no effect on the LH profile. A higher oxytocin dose (20 mIU/g) inhibited LH release when treatment was begun at 05.00, 07.00 or 09.00 h of pro-oestrus. A lower dose (5 mIU/g) was ineffective in altering LH concentrations. In addition, injections of oxytocin (10 mIU/g) at oestrus, metoestrus or dioestrus had no effect on the release of LH. Thus the efficacy of oxytocin in altering concentrations of LH was dose dependent and also critically affected by the day of the oestrous cycle and the time of pro-oestrus. Removal of endogenous oxytocin activity by the use of an oxytocin receptor antagonist abolished the pro-oestrous LH surge, indicating that oxytocin is a vital physiological component of the LH-releasing mechanism in rats. The study provides unequivocal evidence that oxytocin induces LH release in vivo, but the manifestation of oxytocin activity is dependent upon conditions of exposure.
Journal of Endocrinology (1990) 125, 425–432
P. J. BENTLEY
Analogues of oxytocin contract the rat uterus in vitro more strongly in the presence of 0·5 mm-Mg2+ than in the absence of the ion. This effect can be referred to an increased 'affinity' of the hormone for its receptors. Neither Ca2+ (1 mm), Sr2+ (0·5 mm) nor lower concentrations of Mg2+ (0·1 mm) have this effect. Manganese mm) was more effective than Mg2+ (0·5 mm); the former potentiated the action of 3-valine oxytocin 9·9 times; that of 8-arginine oxytocin 3·3 times and that of 8-isoleucine oxytocin 1·3 times while 0·5 mm-Mg2+ potentiated the same analogues 5·7, 1·9 and 1·1 times, respectively. The results are discussed in relation to the mechanism of action of oxytocin.
T. J. Parkinson, H. J. Stewart, M. G. Hunter, D. S. C. Jones, D. C. Wathes and A. P. F. Flint
Analysis of ovine conceptus RNA by slot blotting, Northern analysis and nested polymerase chain reaction failed to detect oxytocin–neurophysin prohormone mRNA. Probes used hybridized with both the 3' end of the prohormone mRNA and the oxytocin-coding sequence. Northern analysis of bovine and porcine conceptus RNA was also negative, and polymerase chain reaction demonstrated oxytocin–neurophysin mRNA in ovine corpus luteum, but not in human corpus luteum or decidua, or in ovine endometrium. Infusion of oxytocin into the uterine lumen in cyclic ewes between days 9 and 19 or 20 after oestrus failed to prolong the luteal phase of the cycle and had no effect on endometrial oxytocin receptor concentrations or uterine prostaglandin F secretion. Oxytocin administered systematically prevented luteolysis and reduced uterine prostaglandin F secretion. Taken together, these data suggest that blastocyst-derived oxytocin is unlikely to contribute to corpus luteum maintenance in early pregnancy. They are inconsistent with a previous report that the ovine blastocyst synthesizes and secretes oxytocin.
Journal of Endocrinology (1991) 130, 443–449
K. M. Burgess, G. Jenkin, M. M. Ralph and G. D. Thorburn
The effect of RU486, a synthetic progesterone receptor antagonist, on basal uterine prostaglandin (PG) release and release in response to oxytocin injection has been investigated in late-pregnant sheep (days 135–140 of gestation). Fifteen hours after i.m. injection of RU486 (50 mg; n = 5) or vehicle alone (n = 4), bolus injections of oxytocin (50, 500 and 5000 mU) were administered via a uterine artery ipsilateral to the pregnant uterine horn at 2-hourly intervals. Uteroovarian vein concentrations of 13,14-dihydro-15-keto PGF2α (PGFM) and PGE2 were determined before and during oxytocin stimulation. Basal concentrations of both PGFM and PGE2 were significantly (P < 0·001) increased in ewes 15 h after RU486 administration compared with ewes receiving vehicle alone. Concentrations of PGFM, but not PGE2, increased significantly (P < 0·001) following injection of each dose of oxytocin in both treated and untreated animals. The response to oxytocin, measured both as the area under the curve and as the peak height of PGFM release, was significantly (P <0·05) greater in RU486-treated ewes. There was no significant effect of oxytocin on the area or peak height of PGE2 response in either RU486-treated or control animals. These results demonstrate that treatment of late-pregnant ewes with RU486 results in an increase in basal uterine PGFM and PGE2 as well as oxytocin-stimulated PGFM release.
Journal of Endocrinology (1992) 134, 353–360