Induction of precocious puberty in the female rat after chronic naloxone administration during the neonatal period: the opiate 'brake' on prepubertal gonadotrophin secretion

1985 ◽  
Vol 104 (2) ◽  
pp. 299-307 ◽  
Author(s):  
D. J. S. Sirinathsinghji ◽  
M. Motta ◽  
L. Martini

ABSTRACT Studies were undertaken using the opiate receptor antagonist naloxone to examine the hypothesis that endogenous opiates may have a restraining effect on prepubertal gonadotrophin secretion and may be involved in the maturation of the central nervous system mechanisms regulating the onset of puberty in the female rat. Naloxone (2·5 mg/kg) administered intraperitoneally every 6 h to female rats from day 1 to day 10 of postnatal life significantly (P <0·001) advanced the age of onset of puberty assessed in terms of the day of vaginal opening and first oestrus (32·3 ± 0·2 vs 40·8 ± 0·4 days in control saline-treated animals). Animals so treated with naloxone showed significantly (P < 0·001) higher levels of FSH (761·4 ± 87·6 vs 483·8± 57·2 μg/l in control animals) and LH (562·8 ± 57·4 vs 351·3 ± 43·3 μg/l in control animals) at the first late pro-oestrus and a significantly (P < 0·001) higher number of ova released at first oestrus (12·4 ± 0·4 vs 8·1±0·3 in controls). Body weight at first oestrus was significantly (P <0·001) lower in the naloxone-treated animals, an indication that these animals were much younger. The weights (per 100 g body wt) of the ovaries and uteri at the first oestrus were significantly (P <0·01) higher in the naloxone-treated rats than in the controls. However, there were no significant differences in the weights of the adrenals and anterior pituitary glands between the two groups of animals. A study of the cyclic patterns of the neonatally naloxone-treated animals performed for 15 consecutive cycles after the first oestrus showed normal 4- or 5-day cycles similar to those occurring in the saline-treated animals. The lengths of the first and second cycles in the naloxone-treated animals were not significantly different from controls. No significant differences in body weight or in organ weights at oestrus or in the levels of LH and FSH determined during the various stages of the oestrous cycle were found between naloxone- and saline-treated animals when these parameters were examined at 3 months of age. Naloxone had no effect on onset of puberty when administered during the other stages of prepubertal life. The mechanisms by which naloxone acts specifically during the neonatal period to induce precocious puberty are at present not known but are being investigated; they may be related to naloxone-induced alterations in the inhibitory synaptic arrangements between opiatergic and gonadotrophin-releasing hormone (GnRH) neurones, with a resulting decrease in the inhibitory influence exerted by endogenous opioids on GnRH neurones during this period of intense neurological development. The results suggest that the endogenous opiate peptides could play a key role in the central mechanisms which trigger the onset of puberty in the female rat. J. Endocr. (1985) 104, 299–307

1982 ◽  
Vol 92 (1) ◽  
pp. 31-35 ◽  
Author(s):  
P. KRAMER ◽  
H. M. A. MEIJS-ROELOFS

The effect was studied of five daily injections of 50 μg of either 5α-androstane-3α,17β-diol (3α-androstanediol) or its 3β-epimer (3β-androstanediol), starting on day 22 of life, on sexual maturation in female rats. No difference was found in the age and body weight at first oestrus between oil-treated rats and rats treated with either 3α- or 3β-androstanediol. The only difference observed between these groups consisted of the occurrence of a 'pinhole' vaginal opening a few days before oestrus in 50% of the steroid-treated rats; in oil-treated rats immediate full vaginal opening and first oestrus coincided in ten out of 12 rats. Different effects were obtained when the higher dose of 100 μg daily was used; effects were dissimilar in rats treated with 3α- and 3β-androstanediol. If administration of the higher dose of 3β-androstanediol was started on day 22 and continued until the day of full vaginal opening and first oestrus, a significant delay of this first oestrus, preceded by a few days of a 'pinhole' type of vaginal opening, was observed. After administration of the higher dose of 3α-androstanediol a 'pinhole' type of vaginal opening, accompanied by dioestrous-like vaginal smears, was also found, but oestrus did not occur during the period when injections were given. After the injections were stopped on day 45, first oestrus developed within 6 days in all rats. The previous findings of others that administration of 3β-androstanediol to the immature female rat may induce precocious puberty (i.e. precocious vaginal opening and first ovulation) were not confirmed in the present study. Our results indicate that high doses of free 3α-androstanediol, and to a lesser degree 3β-androstanediol, may even delay first ovulation in the rat. A possible interference of 3α-androstanediol with the triggering of the first ovulatory gonadotrophin peaks is discussed.


1993 ◽  
Vol 264 (6) ◽  
pp. E986-E992 ◽  
Author(s):  
J. C. Byatt ◽  
N. R. Staten ◽  
W. J. Salsgiver ◽  
J. G. Kostelc ◽  
R. J. Collier

Recombinant bovine prolactin (rbPRL) or bovine growth hormone (rbGH) was administered to mature female rats (10/treatment group) by daily subcutaneous injection for 10 days. Doses ranged from 7 to 5,000 micrograms/day (0.03-24 mg/kg body wt). Both rbPRL and rbGH increased body weight gain and food intake, but these parameters were increased at lower doses of rbPRL (7-63 micrograms/day) than rbGH (> 190 micrograms/day). Weight gain and food intake were maximally stimulated by 190 micrograms/day rbPRL, whereas maximal increased weight gain was obtained with the highest dose of rbGH (5,000 micrograms/day). Total carcass protein was increased by both hormones; however, protein as a percentage of body weight was unchanged. Similarly, neither rbPRL nor rbGH changed the percentage of carcass moisture. Percentage of body fat was increased by rbPRL but was decreased by rbGH. Weight of the gastrointestinal tract and kidneys was increased by both hormones, but increases were in proportion to body weight gain. These data confirm that ungulate prolactin is a hyperphagic agent in the female rat. In addition, they suggest that, while prolactin stimulates growth in mature female rats, this growth is probably not via a somatogenic mechanism.


1985 ◽  
Vol 109 (2) ◽  
pp. 153-157 ◽  
Author(s):  
Mario Maggi ◽  
Maria Laura De Feo ◽  
Massimo Mannelli ◽  
Giuseppe Delitala ◽  
Gianni Forti

Abstract. We evaluated the gonadotrophin response to acute naloxone administration (10 mg iv) in 4 male patients with isolated hypogonadotrophic hypogonadism (age range 18.5–26 years) before and after pituitary priming with daily infusions of GnRH (25 μg/h for 4 h) for 4 days. A blunted gonadotrophin response to acute GnRH administration (100 μg iv) and a lack of response to naloxone was observed before pituitary priming. After repeated infusions of GnRH, pituitary gonadotrophin responsiveness to GnRH was restored, whilst naloxone still did not affect gonadotrophin levels. Our data suggest that in male isolated hypogonadotrophic hypogonadism 1) the lack of pituitary response to naloxone is not due to pituitary hyporesponsiveness to GnRH; 2) endogenous opioids do not exert any inhibitory influence on GnRH secreting neurons and thus are not involved in the pathogenesis of this disease.


1984 ◽  
Vol 52 (3) ◽  
pp. 515-521 ◽  
Author(s):  
J. A. Martinez ◽  
P. J. Buttery ◽  
J. T. Pearson

1. Testosterone (1 mg/kg body-weight per d) given subcutaneously to female rats increased their growth rate and food conversion efficiency but not their food intake compared with that of the placebo-oil controls. A higher dose of testosterone (10 mg/kg body-weight per d) failed to increase the daily weight gain.2. The increased growth rate of the testosterone-treated rats appeared to occur in the whole body and not specifically in muscle. There were no significant changes in body composition.3. The fractional synthetic rate of gastrocnemius muscle protein was higher in the hormone-treated rats than in controls. This contrasts with previous results for the anabolic agent trenbolone acetate and reflects differences in the mode of action of these two different steroids, both with androgenic properties.


1977 ◽  
Vol 73 (3) ◽  
pp. 497-505 ◽  
Author(s):  
K. BROWN-GRANT ◽  
M. B. TER HAAR

SUMMARY The possible occurrence of long-term changes in gonadotrophin control mechanisms following the administration of oestrogen to adult female rats has been studied. Administration of 2·5 mg oestradiol benzoate (OB) to normal female rats at 60 days of age did not result in failure of ovulation at 120 days of age but significant impairment of the LH and FSH responses to progesterone after ovariectomy and oestrogen priming was observed at 160–180 days of age. Treatment with the same dose of OB at 60 days of rats injected with 10 μg testosterone propionate on Day 4 of postnatal life resulted in an increased incidence of failure of ovulation at 120 though not at 150 days of age but did not further impair the already reduced gonadotrophin response to progesterone at 160–180 days of age. Removal of the ovaries at 60 days of age did not modify the effects of oestrogen given at 60 days of age in either group nor did ovariectomy at 60 days improve the response of neonatally androgen-treated rats to progesterone at 160–180 days of age. The increases in plasma prolactin and TSH levels in response to oestrogen priming after ovariectomy were not affected in any of the experimental groups. The administration of a long-acting oestrogen preparation (oestradiol cyclopentyl propionate, 2·5 mg at 60 days of age) to normal female rats suppressed ovulation and depressed plasma LH and FSH concentrations for at least 90 days; anterior pituitary weights were greatly increased and plasma prolactin concentrations were very high.


2020 ◽  
Vol 21 (4) ◽  
pp. 539-549
Author(s):  
Elpita Tarigan ◽  
Adisti Dwijayanti ◽  
Frans Dhyanagiri Suyatna ◽  
Indra Bachtiar ◽  
Sandy Qlintang ◽  
...  

Currently, mesenchymal stem cells (MSCs) for implementing regenerative medicine in aging become interest in medical research science, especially in degerative disease and other aging problems. This research was aimed to determine the effectiveness of hUC-MSCs on inhibiting the aging process through the lifetime of the rat and the effect of intravenous administration of hUC-MSCs in phisiologycally aging female rat on the blood analysis. This study was used 40 aged female rats with 29-30 months of age divided into four groups with 10 rats each. The control rat group was given physiological NaCl (0.9%) 0.5 mL, and the treated rat group was given hUC-MSCs 1x107 cells/kg body weight in 0.5 mL NaCl 0.9%, was injected intravenously in caudo lateralis tail vein with stratified frequency; one time injection (SC1), three times injections (SC3) and five times injections (SC5). Perifer blood was collected from retro-ortbital sinus vein 30 days before and after injection of hUC-MSCs for hematology and blood chemistry analysis. Based on the results were obtained, it indicated that hUC-MSCs increased the survival of aging rat were in treatment group, life span of rats was extended up to 40 months compared to the average life of control rat aged up to 34±2 months. The injection of hUC-MSCs 1x107 cells/kg of body weight with one, three and five times injection were affected to blood profiles and blood chemistry with correlation were low. The conclusions are hUC-MSCs extend the lifespan of aging rat and were affect the blood in general but in normal range of aging rat, affect in ALT and creatinin as tissue repair and tolerated by aging rat.


2020 ◽  
Author(s):  
Herminio M Guajardo ◽  
Rita J Valentino

ABSTRACTStress-induced activation of locus coeruleus (LC)-norepinephrine (NE) projections to the prefrontal cortex is thought to promote cognitive responses to stressors. LC activation by stressors is modulated by endogenous opioids that serve to restrain LC activation and to facilitate a return to baseline activity upon stress termination. Sex differences in this opioid influence could be a basis for sex differences in stress vulnerability. Consistent with this, we recently demonstrated that μ-opioid receptor (MOR) expression is decreased in the female rat LC compared to the male LC and this was associated with sexually distinct consequences of activating MOR in the LC on cognitive flexibility. Given that the LC-NE system affects cognitive flexibility through its projections to the medial prefrontal cortex (mPFC), the present study quantified and compared the effects of LC-MOR activation on mPFC neural activity in male and female rats. Local field potential (LFPs) were recorded from the mPFC of freely behaving male and female rats before and following local LC microinjection of the MOR agonist, DAMGO or vehicle. Intra-LC DAMGO altered the LFP power spectrum selectively in male, but not female rats, resulting in a time-dependent increase in the power in delta and alpha frequency bands. LC microinfusion of ACSF had no effect in either sex. Together, the results are consistent with previous evidence for decreased MOR function in the female rat LC and demonstrate that this translates to a diminished effect on cortical activity that can account for sex differences in cognitive consequences. Decreased LC-MOR function in females could contribute to greater stress-induced activation of the LC, and increased vulnerability of females to hyperarousal symptoms of stress-related neuropsychiatric pathologies.


2021 ◽  
Author(s):  
Zahra Shaaban ◽  
Amin Tamadon ◽  
Mohammad Reza Jafarzadeh Shirazi ◽  
Mohammad Javad Zamiri ◽  
Amin Derakhshanfar

Abstract Despite the prevalence of polycystic ovary syndrome (PCOS) among childbearing women and the development of many animal models for this syndrome, information on its etiology is still scarce. Intrauterine hyperandrogenic environment may underlie changes at the levels of hypothalamus, pituitary and ovary organization in female offspring, and PCOS later in life. Letrozole, has been shown to mimic reproductive and metabolic characteristics of PCOS in adult rodent models. Therefore, the aim of this research was to assess the condition in a prenatal letrozole-treated rat model. Twenty-eight female rats from dams receiving letrozole at certain doses during late pregnancy were used in the trial. Pregnant Sprague-Dawley rats (n = 21) received letrozole treatment on days 16–18 gestation at doses 1.25, 1.0, 0.75, 0.5, and 0.25 mg/kg body weight (BW). Prenatal letrozole-treatment delayed parturition time and reduced the litter size in pregnant dams (P < 0.0001). Late puberty onset, irregular ovarian cyclicity, increased anogenital distance (AGD), body weight gain, and serum testosterone concentration and reduced estradiol levels (P < 0.0001) were observed in the female offspring of dams receiving 1.25 and 1 mg/kg BW letrozole. Furthermore, Letrozole at 1.25 and 1 mg/kg BW showed increased Rfrp and decreased Gnrh mRNA expression (P < 0.0001). Letrozole treatment at doses 1 mg/kg BW and lower was not feto-toxic. It was concluded that 1 mg/kg BW letrozole may be suggested for prenatal PCOS induction.


1982 ◽  
Vol 95 (2) ◽  
pp. 207-213 ◽  
Author(s):  
Patrizia Limonta ◽  
Roberto Maggi ◽  
Luciano Martini ◽  
Flavio Piva

Thermal lesions were placed in the subcommissural organ (SCO) of female rats with normal cycles and long-term ovariectomized rats. In normal female rats SCO lesions disrupted the oestrous cycle in more than half of the animals, the majority of which entered a state of prolonged dioestrus. In these animals, serum gonadotrophin levels were similar to those of rats with regular cycles on day 2 of dioestrus. In animals in which the oestrous cycle was maintained, a delayed LH surge occurred on the day of pro-oestrus and the pro-oestrous FSH surge was absent. The usual increase in FSH on the day of oestrus was present. Lesions in the SCO did not change the high gonadotrophin levels typical of ovariectomized animals. These results suggested that the SCO may play a role in the control of the cyclic but not the tonic release of the gonadotrophins. In particular, it appears that the SCO might be involved in the regulation of the hypersecretion of FSH during the day of pro-oestrus.


1940 ◽  
Vol 17 (2) ◽  
pp. 164-167
Author(s):  
J. R. GROOME

Males were introduced into the cages of six young female rats, which had been injected with 500γ testosterone propionate daily for 8 days. Oestrus was delayed by from 6 to 12 days and was followed by recurrent pseudo-pregnancies or pregnancy. The young were sexually normal and sex-ratio was not significantly affected. The injections caused vaginal mucification, which disappeared within 6 days. These animals (and six controls) were killed on the 60th day when it was found that: (1) There was no abnormal increase in body weight or in the mammary glands. The ovaries appeared normal. (2) There was hypertrophy of the preputial glands and clitoris-like organ. (3) The uteri of two animals that had been recurrently pseudopregnant, but not pregnant, had the typical plicated progestational appearance of testosterone propionate activation. It is suggested that the delay in conception in all cases was due to the condition of the uterus, which underwent a cycle of pseudopregnancies (possibly initiated by the injections) in the presence of the male, until this cycle was terminated by pregnancy. It is also suggested that the treatment temporarily removes the control of cyclical changes in the accessory organs from the ovary, which may itself retain an undisturbed cycle.


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