Localized actions of progesterone in hypothalamus involve oxytocin

Two ovarian hormones, estradiol and progesterone, which facilitate mating behavior in the female rat by acting on the ventromedial nuclei (VMN) of the hypothalamus, induce changes in oxytocin receptor binding in this brain region. Estradiol induced a 4-fold increase in the oxytocin receptor binding of the VMN and surrounding area and increased the number and immunostaining of oxytocin fibers in an area lateral to the ventral VMN. Progesterone, in estrogen-primed rats, caused the induced oxytocin receptors to spread over the area containing the oxytocin fibers. Infusion of oxytocin into the ventromedial hypothalamus increased the display of lordosis behavior only in females primed with both estradiol benzoate and progesterone. Thus, the sequential actions of two ovarian hormones bring a neuropeptide and its receptors into register and enable the neuropeptide to exert behavioral effects.

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Infusion of Antisense Oligo-deoxynucleotides to the Oxytocin Receptor in the Ventromedial Hypothalamus Reduces Estrogen-Induced Sexual Receptivity and Oxytocin Receptor Binding in the Female Rat

Neuroendocrinology ◽

10.1159/000126689 ◽

1994 ◽

Vol 59 (5) ◽

pp. 432-440 ◽

Cited By ~ 109

Author(s):

Margaret M. McCarthy ◽

Steven P. Kleopoulos ◽

Charles V. Mobbs ◽

Donald W. Pfaff

Keyword(s):

Receptor Binding ◽

Ventromedial Hypothalamus ◽

Oxytocin Receptor ◽

Sexual Receptivity ◽

Female Rat

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Ovarian Steroid Modulation of Oxytocin Receptor Binding in the Ventromedial Hypothalamus

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.1992.tb34368.x ◽

1992 ◽

Vol 652 (1) ◽

pp. 374-386 ◽

Cited By ~ 19

Author(s):

MICHAEL SCHUMACHER ◽

HÉCTOR COIRINI ◽

LORETTA M. FLANAGAN ◽

MAYA FRANKFURT ◽

DONALD W. PFAFF ◽

...

Keyword(s):

Receptor Binding ◽

Ventromedial Hypothalamus ◽

Oxytocin Receptor ◽

Ovarian Steroid ◽

Steroid Modulation

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Oxytocin receptors in rat involuting mammary gland

Canadian Journal of Biochemistry and Cell Biology ◽

10.1139/o83-079 ◽

1983 ◽

Vol 61 (7) ◽

pp. 631-635 ◽

Cited By ~ 18

Author(s):

Melvyn S. Soloff ◽

Michael H. Wieder

Keyword(s):

Alkaline Phosphatase ◽

Mammary Gland ◽

Fold Increase ◽

Myoepithelial Cells ◽

Oxytocin Receptor ◽

Secretory Cells ◽

Specific Marker ◽

Oxytocin Receptors ◽

Pregnancy And Lactation ◽

Receptor Number

Oxytocin-receptor concentrations in the rat mammary gland were determined by Scatchard analyses with [3H]oxytocin. There was about a 100-fold increase in the number of receptors per mammary gland between the 1st day of pregnancy and late lactation. The number of receptors then fell markedly during postweaning mammary regression, but rose again during a second pregnancy and lactation cycle. The changes in oxytocin-receptor number corresponded to changes in alkaline phosphatase activity per mammary gland. These results strongly support data suggesting that alkaline phosphatase, like oxytocin receptors, is a specific marker for mammary myoepithelial cells. Despite the fall in oxytocin-receptor number per mammary gland during postweaning regression, the concentration of receptors, expressed per milligram of protein, increased 10-fold over lactating levels on the 6th day of regression. Thereafter, receptor concentrations declined, but were still elevated about fivefold over lactating levels on the 15th day of regression. It is likely that the increased concentration of receptors was due to a decrease in the relative amount of nontarget secretory cells. The factors that regulate the concentration of oxytocin receptors on mammary myoepithelial cells are presently unknown; however, the involuting mammary system may be practical for obtaining enriched populations of oxytocin-sensitive myoepithelial cells.

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Systemic and local regulation of oxytocin receptors in the rat uterus, and their functional significance

Canadian Journal of Biochemistry and Cell Biology ◽

10.1139/o83-077 ◽

1983 ◽

Vol 61 (7) ◽

pp. 615-624 ◽

Cited By ~ 23

Author(s):

A.-R. Fuchs ◽

S. Periyasamy ◽

M. S. Soloff

Keyword(s):

Spontaneous Activity ◽

Estradiol Benzoate ◽

Inhibitory Effect ◽

Oxytocin Receptor ◽

Oxytocin Receptors ◽

Partial Correlations ◽

Near Term ◽

Nuclear Estrogen Receptor ◽

The Right ◽

Intact Rats

Rats were made unilaterally pregnant by tying the right oviduct on the day after mating, to compare the oxytocin receptor concentrations in a nondistended, nonpregnant uterine horn with those in a distended, pregnant horn. On day 20, they were subjected to bilateral ovariectomy and indwelling balloons were inserted into both uterine horns. Following ovariectomy, the rats were injected im with either oil, estradiol benzoate (5 μg/rat per 24 h), progesterone (5 mg/rat per 24 h), or estradiol and progesterone together. For comparison, intact rats were studied on days 21 and 22, 24 and 48 h after insertion of the indwelling balloons. Spontaneous uterine activity and the response to increasing amounts of oxytocin were recorded 20–24 h and 44–48 h after surgery, following which the uteri were excised and assayed for oxytocin and estrogen receptors. The oxytocin receptor concentrations in the two horns were different on day 20 before the treatments were begun, the distended pregnant horn having a higher concentration per milligram DNA than the nonpregnant horn. The various treatments always changed the oxytocin receptor concentrations in the same direction; estrogen increased and progesterone inhibited the estrogen-induced rise in oxytocin receptor concentrations. In intact rats, the distention-induced increase in oxytocin receptor concentrations present on day 20 disappeared near term, but in the absence of the ovaries distention of the uterus had a significant influence on the myometrial oxytocin receptor concentrations, potentiating the effect of estrogen. Progesterone selectively inhibited the distention-induced increase in oxytocin receptor concentrations without inhibiting the hypertrophic effect of distention in general. A good correlation between oxytocin receptor numbers and tissue responsiveness was observed in all instances. The changes in spontaneous activity induced by the various treatments were distinct from the changes in oxytocin responsiveness. Estrogen exerted a strong inhibitory action on the activity stimulated by hormone withdrawal, while progesterone had no inhibitory effect. The pregnant distended horn always showed more spontaneous activity than the nonpregnant horn. There was an overall significant correlation between nuclear estrogen receptor and oxytocin receptor concentrations per milligram DNA, although the partial correlations were not significant in all groups (oil and progesterone). It is concluded that ovarian hormones exert the major regulatory influence on myometrial oxytocin receptor concentrations, but other factors including distention modulate their effect.

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Effects of food deprivation on induction of neural progestin receptors by estradiol in Syrian hamsters

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1996.270.5.r978 ◽

1996 ◽

Vol 270 (5) ◽

pp. R978-R983 ◽

Cited By ~ 2

Author(s):

Y. Du ◽

G. N. Wade ◽

J. D. Blaustein

Keyword(s):

Food Deprivation ◽

Receptor Binding ◽

Preoptic Area ◽

Estradiol Benzoate ◽

Ventromedial Hypothalamus ◽

Metabolic Inhibitors ◽

Binding Assays ◽

Syrian Hamsters ◽

Progestin Receptor

Food deprivation, as well as treatment with metabolic inhibitors, suppress steroid hormone-induced estrous behavior in ovariectomized (OVX) Syrian hamsters. Previous work indicates that 48 h of food deprivation decreases the number of detectable estrogen receptor immunoreactive (ERIR) cells in the ventromedial hypothalamus (VMH) and the area just lateral to it (VLH), increases the number of ERIR cells in the medial preoptic area (MPO), and has no effect on the number of ERIR cells in the nucleus of the solitary tract in OVX hamsters. The present study examined the effects of food deprivation on neural progestin receptor binding using an in vitro binding assay and on progestin receptor immunoreactivity (PRIR) in estradiol-primed, OVX hamsters. Parallel behavior tests for sexual behavior were also performed in both experiments. OVX hamsters received 2.5 micrograms estradiol benzoate and were fed ad libitum or food deprived at the same time. Forty-eight hours later, animals were killed in preparation for the immunocytochemistry or progestin receptor assay. Binding assays indicated that 48-h food deprivation decreased progestin receptor levels in the preoptic area and had no effect in the mediobasal hypothalamus, an area that includes the VMH and the arcuate nucleus (ARH). Immunocytochemical analysis confirmed these findings. Food deprivation caused a decrease in sexual receptivity and in the number of detectable PRIR cells in the MPO and medial amygdala but had no effect on the number of detectable PRIR cells in the VMH/VLH, the ARH, or the anteroventral periventricular nucleus. These results suggest that food deprivation modulates progestin receptor binding and PRIR in a site-specific manner. In addition, the effects of food deprivation on neural ERIR and PRIR are significantly different.

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Selective Oxytocin Receptor Activation in the Ventrolateral Portion of the Ventromedial Hypothalamus Is Required for Mating-Induced Pseudopregnancy in the Female Rat

Endocrinology ◽

10.1210/en.2007-1040 ◽

2007 ◽

Vol 149 (2) ◽

pp. 836-842 ◽

Cited By ~ 13

Author(s):

Lesley E. Northrop ◽

Mary S. Erskine

Keyword(s):

Sexual Behavior ◽

Cerebral Spinal Fluid ◽

Receptor Activation ◽

Ventromedial Hypothalamus ◽

Oxytocin Receptor ◽

Spinal Fluid ◽

Female Rats ◽

Female Rat ◽

Female Sexual Behavior ◽

Cervical Stimulation

The ventrolateral region of the ventromedial hypothalamus (VMHvl) plays an essential role in female sexual behavior. Oxytocin (OT) is released from the paraventricular nucleus to downstream sites such as the VMHvl to facilitate female sexual behavior and shows characteristics of a prolactin (PRL)-releasing factor. During mating, vaginal cervical stimulation (VCS) received from a vasectomized male triggers twice-daily PRL surges that persist up to 12+ d, a period known as pseudopregnancy (PSP). To determine whether OT is involved in PSP by acting within the VMHvl, female rats were infused bilaterally with an oxytocin receptor antagonist (OTR-A), a vasopressin receptor-1a antagonist (V1a-A), or artificial cerebral spinal fluid 30 min before mating. All females received a sufficient amount of VCS, 15 intromissions, to induce PSP. Females infused with OTR-A (20 ng/0.4 μl) with implants targeting the VMHvl showed only a 22% induction of PSP, as measured using vaginal diestrus and serum PRL concentrations. In contrast, controls and V1a-A (80 ng/0.4 μl) infused females exhibited 100% induction of PSP. Females infused with OTR-A returned to estrus after 5 d, whereas females infused with either artificial cerebral spinal fluid or V1a-A remained in diestrus for 12–13 d in both the correct and missed placement groups. Although OT can act as a PRL releasing factor, the PRL surge does not begin until 18–24 h after mating. Together, our results suggest that OT release in the VMHvl mediates the effects of VCS on the induction of the PRL secretion needed to establish PSP.

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The effect of oxytocin and oestradiol on the action of conceptus secretory protein in progesterone-treated ovariectomized ewes

Journal of Endocrinology ◽

10.1677/joe.0.1500473 ◽

1996 ◽

Vol 150 (3) ◽

pp. 473-478 ◽

Cited By ~ 3

Author(s):

G E Mann ◽

J H Payne ◽

G E Lamming

Keyword(s):

Early Pregnancy ◽

Luteal Phase ◽

Protein A ◽

Ovarian Hormones ◽

Secretory Protein ◽

Oxytocin Receptor ◽

Additional Treatment ◽

Secretory Proteins ◽

Oxytocin Receptors ◽

Prostaglandin F

Abstract In intact cyclic ewes intrauterine infusion of conceptus secretory proteins results in the suppression of both endometrial oxytocin receptor concentrations and oxytocin-induced prostaglandin F2α release. However, similar infusion in progesterone-treated ovariectomized ewes, while suppressing endometrial oxytocin receptors, does not fully inhibit oxytocin-induced prostaglandin F2α release. To examine whether this anomaly resulted from an inadequate simulation of the luteal phase in the ovariectomized ewe treated with progesterone alone, the effects of additional treatment with two other ovarian hormones, oestradiol-17β and oxytocin, was investigated. Rather than permitting conceptus secretory protein to successfully inhibit oxytocin-induced prostaglandin F2α release, treatment with oestradiol-17β in addition to progesterone actually resulted in an advancement in the timing of release. However, treatment with oxytocin, alone or in combination with oestradiol, permitted the full inhibition of oxytocin-induced prostaglandin F2α release. To confirm that this effect did not result from the action of oxytocin alone, independently of the action of conceptus secretory protein, a second experiment was undertaken using a similar protocol but without the infusion of conceptus secretory protein. In this situation, oxytocin-induced prostaglandin F2α release was only partially inhibited suggesting that both luteal oxytocin and conceptus secretory proteins are necessary to facilitate the full inhibition of luteolysis during early pregnancy in the ewe. Journal of Endocrinology (1996) 150, 473–478

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