[Experimental studies on the effect of ovarian hormones on the development of rat mandibles].
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
F Döcke
Publications and source records attributed to F Döcke.
Serum levels of FSH, LH and estradiol-17 beta in female rats around the time of puberty onset.
Groups of female rats were autopsied at daily intervals from 27 days of age through the first vaginal cycle and the serum FSH and LH and plasma estradiol-17 beta (E2) concentrations were estimated. Fluctuating hormone concentrations were recorded between days 27 and 31. Both gonadotropins and E2 dropped to a very low level on days 32 and 33 and showed then a progressive increase that commenced on day 34 and terminated for LH and E2 on day 39, i.e. in proestrus, whereas FSH declined from day 37 to day 39. The circulating gonadotropin level was lower during the first postpubertal diestrus than during most of the prepubertal phase. The findings suggest that a high sensitivity to the gonadotropin -inhibiting effect of estrogen prevented completion of an ovarian cycle up to day 33. After that, desensitization to the negative estrogen feedback as indicated by the simultaneous rise of E2 and gonadotropins makes final maturation of ovarian follicles and the first ovulation possible. In part of the rats aged 27-38 days cell nuclear volumes of medial preoptic neurons were evaluated, because recent results suggest that estrogen induces the desensitization process by an inhibitory action on the medial preoptic area. In accordance with this assumption, an inverse relationship between nuclear size and the E2 level in the blood could be revealed.
Animals↗
Evidence that desensitization to the negative estrogen feedback is a prepubertal and not a postpubertal event in female rats.
Female rats were ovariectomized at 31 days of age, on the day of proestrus, or on the day of the first vaginal estrus if corpora lutea were seen in the ovaries. Immediately after castration, estradiol-17 beta (E2) or oil was administered via s.c. silastics capsules, or a 1:240 mixture of estradiol benzoate (EB) and cholesterol or cholesterol alone was unilaterally implanted into the hypothalamic ventromedial-arcuate region. Forty-eight hours after surgery the rats were decapitated and the serum concentrations of LH and FSH estimated. In rats implanted s.c. with E2 in anestrus, proestrus or estrus, estrogen treatment reduced the circulating LH level to 9.4; 60.4 and 33.6% and that of FSH to 49.5; 120.3 and 63%, respectively, of the concentration recorded in the corresponding controls implanted with oil. Following the intrahypothalamic implantation of EB, the serum concentration of LH was lowered to 20.8; 67.4 and 68.1% and that of FSH to 48.8; 87.0 and 62.0% as compared to the cholesterol-implanted controls. The findings clearly suggest that a major part of the change in sensitivity to the negative feedback of estrogen occurs prior to the first preovulatory surge of gonadotrophins.
Anestrus↗
Evidence that inhibition of medial preoptic dopaminergic activity may be involved in the prepubertal desensitization to the negative oestrogen feedback in female rats.
Immature female rats were bilaterally lesioned in the medial preoptic area (MPOA) or hypothalamic ventromedial-arcuate region (VMAR) at 21 days of age and daily injected with the dopamine (DA) agonist bromocriptine (CB-154) through day 26. Estimation of the serum LH and FSH concentrations following ovariectomy and two injections of 0.05 micrograms oestradiol benzoate (OB)/100 g b.w. revealed that the desensitization to the negative feedback effect of OB induced by lesioning of the MPOA was almost completely prevented by CB-154. A similar effect of the drug was not found in rats lesioned in the VMAR. The DA antagonist alpha-methyldopa (alpha-MD) was then bilaterally implanted in the MPOA or VMAR of 28-day-old females. Evaluation of the gonadotrophin-inhibiting effect of OB on days 30-31 showed that medial preoptic, but not hypothalamic implants of alpha-MD reduced the sensitivity to the inhibitory action of OB. It is proposed that diminution of the dopaminergic activity in the MPOA may play a role in the prepubertal desensitization to the negative oestrogen feedback in female rats.
Animals↗
Medial preoptic area, estrogen, and the peripubertal desensitization to the negative estrogen feedback in female rats.
Bilateral lesions placed in the medial preoptic area (MPOA) markedly diminished the luteinizing hormone-(LH-) and follicle-stimulating hormone- (FSH-) inhibiting effects of s.c. injected or intrahypothalamically implanted estradiol benzoate (EB) in ovariectomized immature rats. Desensitization to the negative estrogen feedback was also recorded in immature rats implanted into the MPOA with a mixture of 1 part EB and 240 or 360 parts cholesterol. Estrogen implants located in the hypothalamic ventromedial-arcuate region were ineffective in this regard. Whereas precocious puberty resulted from the implantation of EB into the MPOA, a delay of puberty onset was induced by medial preoptic implants of the antiestrogen clomiphene citrate which also enhanced the LH-suppressing effect of s.c. administered EB in prepubertal females. It is proposed that an increase of the estrogen concentration in the MPOA inactivates medial preoptic neurons that exert a restraining influence on tonic LH (and FSH) secretion by sensitizing the mediobasal hypothalamus to the negative feedback action of estrogen. This mechanism may be involved in the control of the onset of puberty in female rats.
Animals↗
Varying sensitivity to the negative oestrogen feedback during the ovarian cycle of female rats: evidence for the involvement of oestrogen and the medial preoptic area.
The gonadotrophic response to a single injection of oestradiol benzoate (OB) was studied in acutely ovariectomized adult rats during the different stages of a 4-day ovarian cycle. The results showed a sudden decline of the sensitivity to the gonadotrophin-inhibiting effect of OB between metoestrus and dioestrus. This desensitization to the negative oestrogen feedback was probably caused by an oestrogen action on the medial preoptic area (MPOA). In rats ovariectomized and implanted with OB in the MPOA in metoestrus, an s.c. injection of OB on the presumptive day of pro-oestrus did not lower the circulating LH and FSH levels, whereas a clear suppression of gonadotrophin secretion was seen in females implanted with cholesterol in the MPOA or implanted with OB in the hypothalamic ventromedial-arcuate region. Similar findings were obtained in rats which had been ovariectomized 3-4 weeks before implantation. A final experiment demonstrated that bilateral lesioning of the MPOA also reduced the sensitivity to the negative feedback action of oestrogen in long-term ovariectomized rats. In all experiments performed, diminution of the oestrogen-induced inhibition of LH secretion was more marked than that of suppression of FSH secretion. It is proposed that desensitization to the negative oestrogen feedback, probably resulting from an inhibitory oestrogen action on medial preoptic neurones, is a prerequisite for adequate gonadotrophic support of preovulatory follicle maturation in the presence of a continuously rising oestrogen concentration in the blood.
Animals↗
[Significance and mechanism of desensitization to the gonadotropin-inhibiting effect of estrogen. 1. Studies on prepubertal desensitization].
In immature female rats, both a distinctive diminution of the gonadotrophin-inhibiting effect of s. c. or intrahypothalamically implanted estradiol and a simultaneous rise of the estrogen and gonadotrophin levels in the blood were revealed during the last days preceding the onset of puberty. Based on these findings, studies on the neurohormonal mechanism underlying this prepubertal desensitization to the negative estrogen feedback were performed. Bilateral lesioning of the medial preoptic area (MPOA) which induced precocious puberty also diminished significantly the gonadotrophin-inhibiting effect of s. c. or intrahypothalamically administered estrogen. Similar responses were recorded following the implantation of very low quantities of estrogen into the MPOA, whereas medial preoptic implants of the antiestrogen clomiphene citrate impaired the spontaneous prepubertal desensitization and delayed the onset of puberty. It is concluded from the results that the prepubertal increase of the estrogen concentration in the blood itself induces the desensitization to estrogen by an inhibitory effect on medial preoptic neurons. Preliminary clinical and experimental findings suggest that a comparable mechanism may be operative in humans, too.
Animals↗
Effects of rostro-dorsal deafferentation of the hypothalamus on the onset of puberty in female rats.
Rostro-dorsal deafferentation of the hypothalamus by means of the preoptic-roof cut was performed in immature female rats at 17, 21 or 25 days of age, and the onset of puberty was recorded in these and in sham-deafferentated females. A significant delay of vaginal opening and the first ovulation was found following transection of the stria terminalis and fornix system on day 17 or day 25, whereas treatment on day 21 did not influence the onset of puberty. The findings may be explained on the basis of former results obtained after lesioning of the medial amygdala or ventral hippocampus at different ages. They suggest that the puberty-advancing effect of hypothalamic lesions does not depend upon the interruption of afferents from extrahypothalamic structures, but may be caused by the destruction of hypothalamic neurons and/or intrahypothalamic fibres.
Animals↗
Increase of FSH secretion in immature female rats following lesioning of the medial amygdaloid nucleus.
Immature female rats were bilaterally lesioned or sham-lesioned in the anterior part of the medial amygdaloid nucleus (AMN) at 21 days of age, and the serum FSH and LH concentrations were estimated in groups of rats autopsied at daily intervals from day 21 through day 28. Whereas the LH concentration did not differ between lesioned females and the controls, a highly significant elevation of the circulating FSH level was recorded in the lesioned rats from day 22 till day 24. A further experiment demonstrated that similar lesions did not change the FSH and LH-inhibiting effect of estrogen in rats that were ovariectomized on day 22, daily injected with 0.05 microgram estradiol benzoate per 100 g b.w. on days 22 and 23, and sacrificed 24 hr after the last injection. The results suggest that the AMN exerts a restraining influence on the hypophyseal FSH secretion around 21 days of age, and that this inhibitory activity does not depend upon sensitization to the negative feed-back of estrogen.
Amygdala↗
Perisuprachiasmatic lesions enhance the increase of gonadotropin secretion in acutely ovariectomized rats.
Diestrous female rats were bilaterally lesioned in the perisuprachiasmatic region (peri-SCN region) or in the medial preoptic area (MPOA) and ovariectomized immediately after lesioning. Blood was collected at one hour before and at 4.24 and 48 h after surgery. Radioimmunological determination of the serum gonadotropin concentrations revealed that lesioning of the peri-SCN region enhanced significantly the castration-induced increase of FSH and LH secretion at 4 and 24 h, whereas MPOA lesions did not influence the serum hormone levels as compared to the sham-lesioned controls. The findings suggest that the peri-SCN region, but not the MPOA may be involved in the control of the increase of gonadotropin secretion following ovariectomy in rats.
Animals↗
The limbic system and female sexual maturation.
Explore the source record for details and available documents.
Age Factors↗
Further studies on the hypothalamic desensitization to estrogen in immature female rats: evidence for a possible role in the control of puberty.
Immature and puberal female rats were ovariectomized and implanted with estradiol benzoate and cholesterol at the ratios of 1:120 or 1:240 into the hypothalamic ventromedial-arcuate region at 26 or 32 days of age, or on the day of the first vaginal estrus. Evaluation of the serum LH and FSH concentrations on the 2nd day after implantation revealed that the gonadotropin-inhibiting effect of the locally administered estrogen decreased between days 26 and 32 and showed a further distinct decline at the time of puberty. In a second experiment, uterine weight and serum LH and FSH levels were monitored in untreated immature female rats at daily intervals from 25 to 36 days of age. Relatively high values for both gonadotropins were recorded between days 25 and 28. Accelerated uterine growth around day 30 indicating increasing estrogen secretion was associated with a sudden decrease of LH and FSH concentration in the blood. After that, LH and, to a less degree FSH levels began to rise in spite of further weight gain of the uterus. The results suggest that the hypothalamic sensitivity to the gonadotropin-inhibiting effect of estrogen declines during the last week before the onset of puberty. Together with other findings they furthermore indicate that this desensitization process may be involved in the neurohormonal control of puberty in female rats.
Animals↗
Failure to demonstrate a significant influence of ovarian maturity on the onset of puberty in female rats.
Ovaries of 23- and 35-day-old rats were transplanted under the kidney capsules of 31- and 23-day-old females, respectively. The recipient rats were ovariectomized on the fourth day after transplantation, and the onset of puberty was recorded. Neither the age and body weight at vaginal opening and first ovulation nor the length of the first ovarian cycle differed significantly between the experimental rats and sham-transplanted or untreated controls. Estimation of the serum FSH an LH concentrations before and after ovariectomy provided no evidence that different gonadotropic responses had masked puberty-delaying or puberty-advancing effects of the implanted immature and prepuberal ovaries, respectively. The results suggest that the developmental stage of the ovaries is not a decisive factor in the control of the onset of female puberty.
Animals↗
Influence of neonatal ovariectomy on the developmental patterns of serum gonadotropins, hypothalamic LH-RH concentration and organ weights in female rats.
Explore the source record for details and available documents.
Adrenal Glands↗
Estrogen and the puberty-advancing effect of hyperprolactinemia in female rats.
Female Wistar rats were twice daily injected with 10 IU prolactin from 21 days of age to vaginal opening (VO). Precocious VO and ovulation followed by an ovarian cycle of normal length were recorded following this treatment. Hyperprolactinemia induced by the implantation of one pituitary under the kidney capsule of 23-day-old females resulted in advancement of VO but, probably due to the antiovulatory and luteotropic effects of the permanently elevated prolactin levels, the first ovulation occurred only at the normal time of puberty onset, and the first ovarian cycle was significantly lengthened. An increase uterine but not of ovarian weight was induced by both treatments indicating enhanced estrogen secretion. Daily injections of 0.05 or 0.1 microgram estradiol benzoate per 100 g b.w. administered during different periods between day 21 and VO, however, were ineffective in accelerating sexual maturation. The findings suggest that the puberty-advancing effect of hyperprolactinemia does not primarily depend upon the stimulation of ovarian estrogen secretion.
Animals↗
[Caryovolumetrically demonstrable relationship between activity of the hippocampus and sexual maturation in female rats (author's transl)].
Caryovolumetric investigation of hippocampal neurons performed in intact female rats at 21, 26, 32 and 36 days of age, and on the day of the first vaginal estrus revealed distinct prepubertal changes of nuclear volumes of pyramidal neurons located in the ventral hippocampus close by the subiculum. The caryovolumetrically demonstrable activity of these neurons increased significantly between days 21 and 26 and showed a subsequent decrease up to day 36. It was again significantly enhanced at the time of the first vaginal estrus. In contrast to the ventral hippocampus, neuronal activity of the dorsal hippocampus was at a constant level throughout the prepubertal development. Neonatal ovariectomy reduced significantly the nuclear volumes in both hippocampal regions and, simultaneously, prevented completely the prepubertal fluctuation of neuronal activity recorded in the ventral hippocampus of intact rats. The results suggest that the prepubertal activity of hippocampal neurons depends on the integrity of the cerebro-hypophyseo-gonadal axis. They furthermore support the conclusion derived from experimental studies that the hippocampus may be involved in the neurohormonal control of female puberty.
Animals↗
Effects of neonatal pyridostigmine treatment on sexual maturation and adult behaviour in female rats subjected to maternal deprivation.
The present study deals with the effects on adult behaviour of early postnatal maternal, i.e. psychosocial and/or nutritional deprivation and of altering the brain levels and/or turnover rates of acetylcholine in preweaning deprived rats. The following data were obtained: 1. Female rats separated from their mothers and littermates for 16 hours each day during the first two weeks of life showed a significant delay of puberty onset in comparison with non-separated controls. Furthermore, these animals exhibited significantly reduced emotionality as well as learning capability and memory capacity in adulthood. 2. Administration of the acetylcholinesterase inhibitor pyridostigmine during the first two weeks of life to the deprived females did not compensate the puberty-delaying effect of separation. However, the neonatally pyridostigminized female rats exhibited an increased emotional reactivity in adult life. 3. Female rats deprived from their mothers and treated with pyridostigmine during the neonatal period displayed increased avoidance learning and memory capacity in adulthood as compared to neonatally deprived but untreated animals. It might be concluded from our results that defects of brain differentiation produced by early postnatal deprivation could be prevented, at least in part, by simultaneous administration of pyridostigmine.
Acoustic Stimulation↗
[Karyovolumetric studies on the pre-pubertal differentiation of the nucleus infundibularis in female rats].
Cell nuclear volumes of neurons located in the hypothalamic arcuate nucleus were measured in immature female rats autopsied at 21, 26, 32 or 36 days of age, or on the day of the first vaginal estrus. As opposed to limbic cell nuclei measured at the same ages in a former study (DOCKE aND SMOLLICH 1978), significant age-dependent changes of nuclear volumes could not be revealed with the exception of a continuous slight increase during the period of investigation. Neonatal ovariectomy whereas this treatment induced distinct activation of limbic neurons as recorded in a previous experiment (SMOLLICH et al. 1978). It is suggested that the puberty-controlling functions of the arcuate nucleus and of limbic structures depend on different mechanisms.
Animals↗