Effects of 5-hydroxytryptamine uptake blockers on the release of LH and prolactin in several different experimental steroid models in the rat

1985 ◽  
Vol 104 (3) ◽  
pp. 397-406 ◽  
Author(s):  
A. M. Horn ◽  
G. Fink
Keyword(s):  
Single Injection ◽  
Experimental Models ◽  
Prolactin Secretion ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Simultaneous Occurrence ◽  
Lh Surge ◽  
5 Ht Uptake ◽  
Uptake Blockers

ABSTRACT The effect of the 5-hydroxytryptamine (5-HT) uptake blockers on the surges of LH and prolactin has been investigated in pro-oestrous rats and various experimental models used frequently to study the effects of steroids on LH and prolactin secretion in female rats. The steroid models were: rats ovariectomized on dioestrus, injected immediately with oestradiol benzoate (OB) and at 12.00 h on the next day (presumptive pro-oestrus) with progesterone (model 1); long-term ovariectomized rats injected with a single injection of OB and 72 h later with either progesterone (model 2) or OB (model 3); long-term ovariectomized rats injected daily with OB (model 4). The uptake blockers alaproclate (3–30 mg/kg) and zimelidine (20 mg/kg) were injected and blood samples withdrawn from previously implanted intra-atrial cannulae. Plasma LH and prolactin concentrations were determined by radioimmunoassay. The present study confirmed that a surge of LH occurs at about 17.00–18.00 h of the presumptive day of pro-oestrus in model 1, at about 5 h after (∼ 17.00 h) the injection of either progesterone or the second injection of OB in models 2 and 3, and diurnally in model 4, and the simultaneous occurrence of a prolactin surge in models 2 and 4. A surge of prolactin at the same time as the LH surge was shown to occur also in models 1 and 3. Alaproclate (30 mg/kg) administered at 15.00 h delayed significantly the peak of the prolactin surge in the pro-oestrous rat and models 1, 3 and 4, and in the latter the magnitude of the prolactin surge was also significantly reduced. By contrast, the peak of the prolactin surge in model 2 was significantly prolonged by alaproclate. Alaproclate had no significant effect on either the timing or the magnitude of the LH surge in the pro-oestrous rat, and models 3 and 4. The peak of the LH surge was delayed by alaproclate in model 1 and abolished in model 2, providing further evidence for the possible importance of interactions between 5-HT and progesterone in neuroendocrine control. Zimelidine had no significant effect on either the LH or prolactin surge in the pro-oestrous rat and in models 1 and 2. These results show that normal 5-HT uptake is necessary for the normal timing and/or magnitude of the spontaneous and steroid-induced prolactin surge but is not essential for the normal timing and magnitude of the spontaneous surge of LH and the LH surge in some but not all steroid models. In terms of neuroendocrine effects alaproclate is more potent than zimelidine. The different effects of alaproclate in the different steroid models suggest that although superficially similar, different mechanisms underlie the prolactin and LH surges in these steroid models. J. Endocr. (1985) 104, 397–406

ALTERATIONS INDUCED BY CLOMIPHENE IN THE CONCENTRATIONS OF OESTROGEN RECEPTORS IN THE UTERUS, PITUITARY GLAND AND HYPOTHALAMUS OF FEMALE RATS

1980 ◽  
Vol 87 (3) ◽  
pp. 383-392 ◽  
Author(s):  
E. Y. ADASHI ◽  
A. J. W. HSUEH ◽  
S. S. C. YEN
Keyword(s):  
Pituitary Gland ◽  
Nuclear Receptors ◽  
Single Injection ◽  
Clomiphene Citrate ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Oestrogen Receptors ◽  
Prolonged Retention

Alterations in the concentrations of oestrogen receptors in the uterus, pituitary gland and hypothalamus during the 2 weeks following a single administration of clomiphene citrate (Clomid) to immature, bilaterally ovariectomized rats were investigated. Examination of the uterine wet weight at 1, 7 and 14 days following a single injection of Clomid (100 μg, 250 μg or 10 mg) indicated significant time- and dose-related increments from a control value of 45 ± 2 (s.e.m.) mg to a maximum of 123 ± 3 mg (250 μg dose at 14 days). In contrast, a single injection of oestradiol led to a transient increase in the uterine weight on day 1 to 94 ± 6 mg, but was without effect by days 7 and 14. Analysis of the uterine DNA content 7 and 14 days after treatment with Clomid revealed significant increments from control values of 390 ± 10 μg to a high level of 558 ± 8 μg (10 mg dose at 7 days). There was a transient retention of nuclear oestrogen receptors and rapid replenishment of cytoplasmic oestrogen receptors in less than 24 h in the uteri of animals treated with oestradiol (25 μg), but determinations of receptor content in Clomid-treated animals revealed prolonged retention of nuclear receptors and delayed replenishment of cytoplasmic receptors. The duration and extent of retention of nuclear receptors and depletion of cytoplasmic receptors after treatment with Clomid were found to be dose-dependent. Fourteen days after Clomid treatment, levels of oestrogen receptors in nuclei from the uterus were still raised in all treatment groups, whereas replenishment of cytoplasmic receptors was complete in animals treated with the lower doses (100 and 250 μg) of Clomid. A single injection of Clomid (250 μg) induced similar prolonged retention of nuclear receptors and delayed depletion of cytoplasmic receptors in pituitary tissue. In contrast, changes in the content of oestrogen receptors in the hypothalamus following Clomid treatment were minimal. The limited effect of Clomid on hypothalamic tissue may mean that the pituitary gland is a more important target for this compound than is the hypothalamus. The findings have confirmed earlier reports on the long-term uterotrophic effect of Clomid and have suggested that under these long-term, in-vivo conditions, Clomid acts in the uterus and pituitary gland as a long-acting oestrogen characterized by prolonged retention of oestrogen receptors in the nucleus and delayed, but otherwise effective, replenishment of the oestrogen receptors in the cytoplasm.

OESTROGEN AND PROGESTERONE INFLUENCE ON THE RELEASE OF PROLACTIN IN OVARIECTOMIZED RATS

1974 ◽  
Vol 60 (2) ◽  
pp. 205-215 ◽  
Author(s):  
L. CALIGARIS ◽  
J. J. ASTRADA ◽  
S. TALEISNIK
Keyword(s):  
Single Injection ◽  
Prolactin Secretion ◽  
Male Rats ◽  
Ovariectomized Rats ◽  
Serum Prolactin ◽  
Inhibitory Effects ◽  
Oestradiol Benzoate ◽  
Close Relationship ◽  
Dose Dependent

SUMMARY The concentration of prolactin in serum after oestrogen and progesterone injection into spayed rats was measured by radioimmunoassay. After a single injection of 5 μg oestradiol benzoate (OB) into long-term ovariectomized rats, serum prolactin concentrations showed a circadian rhythm with high levels in the afternoon and almost no changes in the morning. Peaks of prolactin occurred 2, 3 and 4 days after the injection. Below a dose of 1 μg OB, the response was dose-dependent, but the response was then maximal. In spayed rats primed with 5 μg OB, the injection of 2 mg progesterone 2, 3 or 4 days later resulted in a significant increase in serum prolactin. This response, in contrast to that of oestrogen, occurred in the morning and in the evening and was found to be dose-dependent. The rise in serum prolactin after injection of 1 mg progesterone also showed a close relationship to the priming dose of OB. Progesterone had no effect in spayed, untreated animals. Maximal levels of prolactin were attained 3–4 h after the s.c. injection of progesterone. The release of prolactin which can be induced either by OB or by progesterone was blocked by the administration of progesterone injected 1 day before the expected release would occur. These results indicate that progesterone exerts both facilitatory and inhibitory effects on prolactin secretion. Male rats were found to be less sensitive to the ovarian steroid treatment. It is suggested that oestrogen could be responsible for the rise in prolactin observed at pro-oestrus and progesterone for the increase in prolactin in pseudopregnancy and pregnancy.

scholarly journals The Increase in Signaling by Kisspeptin Neurons in the Preoptic Area and Associated Changes in Clock Gene Expression That Trigger the LH Surge in Female Rats Are Dependent on the Facilitatory Action of a Noradrenaline Input

Endocrinology ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 323-335 ◽  
Author(s):  
Bruna Kalil ◽  
Aline B. Ribeiro ◽  
Cristiane M. Leite ◽  
Ernane T. Uchôa ◽  
Ruither O. Carolino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Median Eminence ◽  
Preoptic Area ◽  
Clock Genes ◽  
Third Ventricle ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Lh Surge ◽  
Clock Gene Expression

Abstract In rodents, kisspeptin neurons in the rostral periventricular area of the third ventricle (RP3V) of the preoptic area are considered to provide a major stimulatory input to the GnRH neuronal network that is responsible for triggering the preovulatory LH surge. Noradrenaline (NA) is one of the main modulators of GnRH release, and NA fibers are found in close apposition to kisspeptin neurons in the RP3V. Our objective was to interrogate the role of NA signaling in the kisspeptin control of GnRH secretion during the estradiol induced LH surge in ovariectomized rats, using prazosin, an α1-adrenergic receptor antagonist. In control rats, the estradiol-induced LH surge at 17 hours was associated with a significant increase in GnRH and kisspeptin content in the median eminence with the increase in kisspeptin preceding that of GnRH and LH. Prazosin, administered 5 and 3 hours prior to the predicted time of the LH surge truncated the LH surge and abolished the rise in GnRH and kisspeptin in the median eminence. In the preoptic area, prazosin blocked the increases in Kiss1 gene expression and kisspeptin content in association with a disruption in the expression of the clock genes, Per1 and Bmal1. Together these findings demonstrate for the first time that NA modulates kisspeptin synthesis in the RP3V through the activation of α1-adrenergic receptors prior to the initiation of the LH surge and indicate a potential role of α1-adrenergic signaling in the circadian-controlled pathway timing of the preovulatory LH surge.

scholarly journals Pup removal suppresses estrogen-induced surges of LH secretion and activation of GnRH neurons in lactating rats

2006 ◽  
Vol 191 (1) ◽  
pp. 339-348 ◽  
Author(s):  
Atsushi Fukushima ◽  
Ping Yin ◽  
Maho Ishida ◽  
Nobuhiro Sugiyama ◽  
Jun Arita
Keyword(s):  
Third Ventricle ◽  
Acute Effect ◽  
Suppressive Effect ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Indwelling Catheter ◽  
Lh Surge ◽  
Gnrh Neurons ◽  
Double Immunohistochemical Staining ◽  
Lh Secretion

During lactation, the suckling stimulus exerts profound influences on neuroendocrine regulation in nursing rats. We examined the acute effect of pup removal on the estrogen-induced surge of LH secretion in ovariectomized lactating rats. Lactating and nonlactating cyclic female rats were given an estradiol-containing capsule after ovariectomy, and blood samples were collected through an indwelling catheter for serum LH determinations. In lactating, freely suckled ovariectomized rats, estrogen treatment induced an afternoon LH surge with a magnitude and timing comparable to those seen in nonlactating rats. Removal of pups from the lactating rats at 0900, 1100, or 1300 h, but not at 1500 h, suppressed the estrogen-induced surge that normally occurs in the afternoon of the same day. The suppressive effect of pup removal at 0900 h was completely abolished when the pups were returned by 1400 h. In contrast, pup removal was ineffective in abolishing the stimulatory effect of progesterone on LH surges. Double immunohistochemical staining for gonadotropin-releasing hormone (GnRH) and c-Fos, a marker for neuronal activation, revealed a decrease, concomitantly with the suppression of LH surges, in the number of c-Fos-immunoreactive GnRH neurons in the preoptic regions of nonsuckled rats. An LH surge was restored in nonsuckled rats when 0.1 μg oxytocin was injected into the third ventricle three times at 1-h intervals during pup removal. These results suggest that the GnRH surge generator of lactating rats requires the suckling stimulus that is not involved in nonlactating cyclic female rats.

Cyclophenil, a non-steroidal compound with a higher central than peripheral oestrogenic activity: study of its effects on uterine growth and on some central parameters in castrated female rats

1984 ◽  
Vol 107 (3) ◽  
pp. 340-345 ◽  
Author(s):  
F. Celotti ◽  
N. Avogadri ◽  
R. C. Melcangi ◽  
S. Milani ◽  
P. Negri-Cesi
Keyword(s):  
Prolactin Secretion ◽  
The Other ◽  
Female Rats ◽  
Reliable Estimate ◽  
Growth Test ◽  
Oestradiol Benzoate ◽  
Enzymatic Systems ◽  
Uterine Growth ◽  
Steroidal Compound

Abstract. The oestrogenic activity of cyclophenil, a non-steroidal compound which has structural analogies with both stilbene and triphenylethylene, has been reevaluated utilizing both central and peripheral parameters. The central parameters considered were LH, FSH, prolactin secretion and two enzymatic systems known to be oestrogen-sensitive: hypophyseal 5α-reductase and hypothalamic aromatase. The uterine growth test was used to determine oestrogenic peripheral activity. The compound was administered at various doses in comparison with oestradiol benzoate (EB) to long-term castrated female rats. Cyclophenil has an activity 1/8110 times that of EB on uterine growth, and 1/1660 and 1/550 times that of EB in inhibiting LH and FSH. respectively. The hypophyseal 5α-reductase(expressed as DHT formation) was inhibited 1710 times less by cyclophenil than by EB. The other parameters considered were unsuitable to provide a statistically reliable estimate of the potency ratios between the two compounds. The data show that cyclophenil is an oestrogenic compound with peculiar characteristics. This substance is more effective in expressing its oestrogenic activity in central structures than in the peripheral ones.

Inhibition of phasic but not tonic pituitary secretion by 2-hydroxyoestrone in the rat: evidence of action as an oestrogen antagonist

1983 ◽  
Vol 98 (1) ◽  
pp. 103-112 ◽  
Author(s):  
Shigehiro Katayama ◽  
Jack Fishman
Keyword(s):  
Pituitary Hormones ◽  
Ovariectomized Rats ◽  
Priming Dose ◽  
Physiological Mechanisms ◽  
Lh Surge ◽  
Oestradiol Benzoate ◽  
Pituitary Secretion ◽  
The Brain ◽  
Phasic Release

Rats with 4-day oestrous cycles, implanted with intracardiac catheters, were injected with 2-hydroxyoestrone at noon on pro-oestrus and their plasma LH levels monitored at frequent intervals thereafter. A dose of 100 μg 2-hydroxyoestrone completely abolished the preovulatory LH rise in four out of ten animals tested, showing no effect in the six others. When an injection of 10 μg oestradiol 1 h before the 2-hydroxyoestrone administration was given all the rats showed an absence of the preovulatory LH surge, while it remained intact in the controls treated with oestradiol only. The principal metabolite of 2-hydroxyoestrone, 2-methoxyoestrone, exhibited no influence on the pituitary gonadotrophin release. Repeated injections of 100 pg doses of 2-hydroxyoestrone to long-term ovariectomized rats produced no change in plasma LH and prolactin levels. In animals primed with oestradiol benzoate, 2-hydroxyoestrone given 1–2 h after the priming dose blocked the phasic release of the pituitary hormones on the afternoon of the 2 subsequent days. The LH and prolactin surges in the primed animals, however, were not affected when the catechol oestrogen was injected 2 h before their appearance. These results indicate that in the cyclic rat exogenous 2-hydroxyoestrone inhibits the preovulatory LH surge when its administration is coincident with the preovulatory oestradiol rise. In the ovariectomized rat 2-hydroxyoestrone inhibits the oestrogen-dependent priming step but does not affect either the oestrogen-independent expression of the induced surges or the tonic secretion of these pituitary hormones. These results indicate a dissociation of central and peripheral activities in this oestradiol metabolite and suggest that this catechol oestrogen functions as an oestrogen antagonist in neuroendocrine events. Since catechol oestrogens can be formed in the brain these pharmacological responses may reflect physiological mechanisms.

SENSITIVITY OF ANTERIOR HYPOTHALAMIC AREAS TO GONADAL STEROID IMPLANTATION IN ANDROGENIZED FEMALE RATS

1977 ◽  
Vol 74 (2) ◽  
pp. 315-NP ◽  
Author(s):  
A. DANGUY ◽  
J. L. PASTEELS ◽  
F. ECTORS
Keyword(s):  
Single Injection ◽  
Mammary Glands ◽  
Prolactin Secretion ◽  
Female Rats ◽  
Male Rats ◽  
Control Synthesis ◽  
Normal Female ◽  
Immunofluorescence Studies ◽  
Oestradiol Benzoate ◽  
Stimulation Of

A single injection of 1 mg of a complex of testosterone esters on day 5 of life was used to prepare constantly oestrous rats. Such androgenized female rats were then ovariectomized and submitted to stereotaxical implantation of 1 μg oestradiol benzoate, 5 μg testosterone isobutyrate or, as a control, 10 μg cholesterol in the anterior hypothalamic areas. The effects of the steroids on plasma and pituitary FSH and LH were assessed by radioimmunoassay. As reported previously by us in normal female and male rats, the preoptic–suprachiasmatic area (POA) was able to control synthesis and secretion of both gonadotrophins and did not lose its sensitivity to oestradiol and testosterone in androgenized rats. Evidence for enhanced prolactin secretion in androgenized rats was derived from immunofluorescence studies of the pituitary gland and from histology of the mammary glands. In this respect the condition of the androgenized females was opposite to that of the males. The present work demonstrated that stimulation of prolactin secretion in androgenized female rats resulted from oestrogen action due to permanent oestrus rather than from impairment of hypothalamo-hypophysial relationships. Indeed, prolactin stimulation was suppressed when the androgenized rats were ovariectomized and restored when they were subsequently implanted with oestradiol in the POA.

Development and amplification of mid-afternoon surges of prolactin secretion in ovariectomized immature rats

1986 ◽  
Vol 110 (2) ◽  
pp. 361-366 ◽  
Author(s):  
H. F. Urbanski ◽  
S. R. Ojeda
Keyword(s):  
Prolactin Secretion ◽  
Ovariectomized Rats ◽  
Female Rat ◽  
Plasma Prolactin ◽  
Short Term ◽  
Small Magnitude ◽  
Neuroendocrine Mechanisms ◽  
Phases Of Development ◽  
Juvenile Development

ABSTRACT The immature female rat shows a mid-afternoon surge of prolactin secretion which reaches a maximum on the day of first pro-oestrus. The present experiments were undertaken to elucidate the mechanisms which underly the development of this prolactin discharge. Detailed plasma prolactin profiles were obtained from short-term (48 h) ovariectomized rats at 23, 28 or 37 days of age. In the two older groups, but not the youngest, a mid-afternoon surge of prolactin secretion occurred in spite of the absence of the ovaries. To exclude the possibility that such an apparent ovarian-independent discharge of prolactin was due to an oestradiol effect which persisted for 2 days following ovariectomy, another study was conducted using long-term ovariectomized animals. Plasma profiles were obtained from neonatally ovariectomized rats at ages equivalent to juvenile (26–28 days), peripubertal (38–41 days) or adult (46–49 days) phases of development. A mid-afternoon surge of prolactin secretion was observed in the majority of animals (eight out of twelve) irrespective of the interval after ovariectomy; this finding further indicates that in the female rat there is a centrally originated mid-afternoon episode of prolactin secretion which is expressed during juvenile development even in the absence of the ovaries. The relatively small magnitude of these ovarian-independent prolactin discharges (c.f. the preovulatory prolactin surge) suggested that in the intact animal they are amplified by ovarian secretions. To test this hypothesis, oestradiol-containing silicone elastomer capsules were implanted s.c. into juvenile rats, immediately after ovariectomy, and plasma prolactin profiles examined 2 days later (28 days of age). In all cases the prolactin surge was greatly amplified and in many instances the magnitude was identical to that observed at first pro-oestrus. These data suggest that development of the large pro-oestrous surge of prolactin secretion involves the interplay of at least two distinct neuroendocrine mechanisms: (1) a centrally originated ovarian-independent signal and (2) an amplification effect exerted by ovarian oestradiol. J. Endocr. (1986) 110, 361–366

scholarly journals Effects of long-term treatment with resveratrol and subcutaneous and oral estradiol administration on pituitary function in rats

2006 ◽  
Vol 189 (1) ◽  
pp. 77-88 ◽  
Author(s):  
Martina Böttner ◽  
Julie Christoffel ◽  
Hubertus Jarry ◽  
Wolfgang Wuttke
Keyword(s):  
Serum Levels ◽  
Term Treatment ◽  
Prolactin Secretion ◽  
Gnrh Receptor ◽  
Female Rats ◽  
Pituitary Function ◽  
Ovx Rats ◽  
Long Term Treatment

Hormone replacement therapy (HRT) has been used for several decades to treat menopausal discomforts. However, in the light of recent studies that draw attention to the potential hazards of conventional HRT, various attempts have been undertaken to search for alternatives to classical HRT. Phytoestrogens are claimed to be capable of positively influencing menopausal symptoms, including hot flushes. We designed a long-term study of 3 months to assess the effects of subcutaneous and orally fed 17β-estradiol (E2), as well as the actions of resveratrol (RES) on pituitary function in female rats. Our results have demonstrated that RES binds with a 10-fold lower affinity to estrogen receptor (ER)-α than to ERβ. The data from the in vivo study revealed that a dosage of 5 μg and 50 μg RES/kg bodyweight per day given to ovariectomized (OVX) rats achieved serum levels of 1.0 and 8.1 μM respectively. Long-term treatment of OVX rats with RES revealed no estrogenic potential on pituitary function in vivo as assessed by LH and prolactin secretion and by regulation of mRNAs for LHα, LHβ, and GnRH receptor. Subcutaneous treatment with E2 in silastic capsules exerted stronger effects on LH and prolactin secretion, as well as on LHβ, LHα, GnRH receptor, and ERβ mRNA regulation compared with orally applied estradiol benzoate despite comparable serum levels. Levels of aryl hydrocarbon receptor (AhR) mRNA in the pituitary were increased following OVX and attenuated by long-term E2 treatment, whereas RES did not modulate AhR mRNA expression.

The inhibitory effect of opiates on gonadotrophin secretion is dependent upon gonadal steroids

1984 ◽  
Vol 102 (2) ◽  
pp. 133-141 ◽  
Author(s):  
R. Bhanot ◽  
M. Wilkinson
Keyword(s):  
Negative Feedback ◽  
Prolactin Secretion ◽  
Gonadal Steroids ◽  
Female Rats ◽  
Inhibitory Effects ◽  
Endogenous Opiates ◽  
Gonadotrophin Secretion ◽  
Oestradiol Benzoate ◽  
Lh Secretion

ABSTRACT We have attempted to clarify the physiological involvement of endogenous opiates in the steroid-mediated control of gonadotrophin release. Our studies showed that there was an acute reduction in the inhibitory effects of endogenous opiates on LH and FSH release following gonadectomy in the rat. This was indicated by a significant reduction in the ability of naloxone to stimulate serum LH/FSH levels (sampled at 15 min) in 26-day-old female rats 48 h after ovariectomy. Luteinizing hormone was highly sensitive to the inhibitory effects of the synthetic met-enkephalin analogue, FK 33-824, at this time (sampled at 90 min). An unexpected observation was that long-term absence of gonadal steroids also disrupted the ability of exogenous opiates, FK 33-824 and morphine, to influence LH release. This was seen as an inability of FK 33-824 (1·0 or 3·0 mg/kg) to inhibit LH secretion. The effects of gonadectomy on opiate control of LH occurred at all developmental stages and were not due to a disruption of sexual maturation. Opiate involvement in prolactin secretion did not appear to be adversely affected by an absence of gonadal steroids. Another novel aspect of this work was that the opiatergic component in the control of gonadotrophin secretion could be reinstated in long-term gonadectomized rats by treatment with oestradiol benzoate or testosterone propionate. Similarly, priming with increasing dosages of oestradiol benzoate which resulted in progressively lower LH levels gave larger naloxone responses. This steroid–opiate interdependency suggests that the negative feedback influence of gonadal steroids on LH secretion is conveyed, in part, by hypothalamic opiate peptides. Our results therefore provide a neurochemical basis for gonadal steroid negative feedback. J. Endocr. (1984) 102, 133–141

Sign in / Sign up

Export Citation Format

Share Document