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Biomedical subjects

F Döcke

Publications and source records attributed to F Döcke.

At least 19 recordsLinked to original sources

[Dopamine antagonists in anovulation?].

Increased hypothalamic dopamine turnover may prevent the ovulatory LH peak by different mechanisms and may in this way result in anovulation. Ten patients with anovulatory menstrual cycles who had been treated with clomiphene citrate without success were given the dopaminolytic drug pimozide (Antalon) at a dose of 5 mg/day orally either from day 7 to day 11 (7 women; group 1) or from day 11 to day 15 of the menstrual cycle (4 women; group 2). One patient from group 2 ovulated during the treatment cycle. A further woman from this group exhibited an LH peak, but did not ovulate, whereas a slow increase of the circulating LH level was recorded in the remaining two patients. Systematic investigations should clarify whether introduction of dopaminolytic therapy in the treatment of hypothalamic anovulation may be justified.

Anovulation

[Neurohormonal regulation of male gonad function].

In a survey the neurohormonal regulatory mechanisms are discussed which control the incretory and spermiogenetic function of the testicles in adulthood. The central position of LH-RH and the factors influencing its secretion, the negative feedback between the testicular hormones including inhibin and the hypophyseal gonadotropins as well as the periodic changes superimposed to the basal secretion of the sexual hormones are explained. Finally, the present knowledge is summarized on the cooperation of the different hormones and mechanisms in the regulation of the incretory and excretory testicular functions.

Androgens

Experimental studies on the neurohormonal control of female puberty.

Experiments were performed in rats to study the role played by ovarian estrogens, the hypothalamus, the medicortical amygdala, and the ventral hipopcampus in the neurohormonal control of female sexual maturation. The results obtained demonstrated that the ovulation-inducing effect of a single administration of estradiol benzoate (EB) to immature female rats is not tantamount to the induction of precocious puberty. Long-term treatment with very low doses of EB, however, can accelerate sexual maturation, although it was established that the endogenous ovarian estrogen secretion during prepuberal life is not essential for the maturation of the cyclic ovarian function. Implantation of very low quantities of EB into the mediobasal hypothalamus of ovariectomized immature and postpuberal female rats revealed that the hypothalamic sensitivity to the LH-inhibiting effect of estrogen exhibits a gradual decrease that begins some days prior to the onset of puberty. It may be responsible for a temporary elevation of the LH level in the blood triggering final maturation of the ovarian follicles and an increase of estrogen secretion. - Studies on the influence of the limbic system on female sexual maturation lead to the following conclusions: 1. The mediocortical amygdala has an essential function in the maturation of the positive estrogen feedback. 2. An LH-inhibiting activity not related to the negative estrogen feedback is exerted by this nuclear region during critical periods of sexual maturation. It may form an additional protective mechanism against precocious stimulation of the ovaries. 3. By means of its stimulatory action on growth hormone and FSH secretion, the ventral hippocampus may be involved, by cholinergic mechanisms, in the interrelationships between metabolism and the onset of female puberty. The results which suggest a significant role of the limbic system in the control of female sexual maturation will be discussed with regard to recent data obtained in girls and women.

Animals

[Animal experiment studies on the neurohumoral control of female puberty].

To study the mode of action of oestrogen in female sexual maturation, prepubertal female rats were treated in different ways with oestradiol benzoate (OB). Using an improved implantation method, former findings on a hypophysial site of oestrogen action in the positive feedback (Hohlweg effect) were confirmed. A single s.c. injection or intrahypophysial implantation of OB at 25 or 26 days of age induced precocious vaginal opening (VO) and one ovulation, but the subsequent ovarian cycle was significantly prolonged, so that the first spontaneous ovulation occurred only at the normal time of the onset of puberty. Further studies demonstrated that the sensitivity to the ovulation-inducing effect of oestrogen increases as the rats approach the age of puberty, and that the first pubertal ovulation can be suppressed by intrahypophysial, but not by intrahypothalamic implantation of progestereone. The conclusion is drawn that the precocious induction of one ovulation via the Hohlweg effect is not tantamount to an advancement of puberty. The results furthermore suggest that the positive oestrogen feedback forms the basis for the first pubertal ovulation as it does with regard to later cyclic ovulations. True acceleration of sexual maturation was achieved by daily injections of 0,05 microgram OB/100 g b.w. from 5 days of age to VO. In contrast to findings obtained by other authors in Sprague-Dawley rats, a shortened OB treatment from 26 days of age to VO was not effective in advancing the onset of puberty unless the rats had additionally been injected with OB from 5 to 10 days of age. A final experiment demonstrated that the first ovarian cycle was not prolonged after neonatal ovariectomy and implantation of ovaries at 24, 28 or 32 days of age. Thus, maturation of the neurohormonal mechanisms that are responsible for the cyclic ovarian function continues during the prepubertal development in the absence of ovarian steroids.

Age Factors

[Animal experiment studies on the neurohumoral control of female puberty. 2. Studies on the influence of amygdala and of the hippocampus on sex maturation].

Immature female rats were bilaterally lesioned in the rostral or caudal part of the mediocortical amygdala (MCA) or in the ventral hippocampus (VHPC) at 21 days of age. In a second experiment, simultaneous lesioning of the MCA or VHPC and the medial preoptic area or hypothalamic ventromedial-arcuate region was performed in 21-day-old rats. Finally, discrete lesions were placed into the anterior or posterior parts of the medial (MAN) or cortical amygdaloid nuclei ath 21, 26 or 32 days of age. The effects of the different treatments on the onset of puberty were evaluated by recording the age at vaginal opening and first ovulation, the body weight on the day of vaginal opening, and the subsequent ovarian or vaginal cyclicity. The following conclusions may be drawn from the findings obtained: 1. At three weeks of age, the MCA exerts a gonadotropininhibiting function that is localized in the anterior part of the MAN. This activity is not demonstrable in older females. 2. The MAN, particularly its posterior part, may play an important role in the prepuberal maturation of the maturation of the neurohormonal ovulatory mechanisms that takes place in female rats during the fourth week of life. 3. The VHPC may be involved in the control of female sexual development mainly by its growth-stimulating activity. The results suggest an essential role of the subcortical limbic system in female sexual maturation and offer an explanation of contradictory findings on the gonadotrophin-controlling function of the MCA before puberty.

Amygdala

Studies on the time and localization of the puberal desensitization to oestrogen in female rats.

Immature and postpuberal female rats were ovariectomized at 20 or 27 days of age or on the day of the first vaginal oestrus and chronically implanted with oestradiol benzoate (OB) and cholesterol at the ratios of 1 : 60, 1 : 120 or 1 : 240 on the day following castration. Autopsy was performed on day 6 after implantation and the plasma LH concentration determined by radioimmunoassay. Whereas 1 : 60 and 1 : 120 implants of OB and cholesterol placed into the hypothalamic ventromedial-arcuate region depressed the castration-induced elevation of the LH level before and after puberty, the 1 : 240 mixture was effective only in immature rats, but not after vaginal opening and the first ovulation had occurred. A similar trend was recorded after implantation of OB into the cortical amygdaloid nucleus (CAN). However, the oestrogen dose had to be doubled to get comparable results. Bilateral lesioning of the CAN or deefferentation of the mediocortical amygdala by transection of the stria terminalis did not distinctively influence the LH-suppressing effect of daily s.c. injections of 0.1 or 0.05 microgram OB/100 g b. w. in prepuberal rats. The findings demonstrate a sudden change in the hypothalamic threshold to the gonadotrophin-inhibiting effect of oestrogen over a narrow range of time near the onset of puberty. They furthermore suggest that the mediocortical amygdala is not involved in possible extra-hypothalamic control of the puberal desensitization process.

Animals

Morphological differentation of limbic nuclei during sexual maturation of female rats.

Cell nuclear volumes were measured in the central parts of the medial amygdaloid nucleus (MAN), cortical amygdaloid nucleus (CAN) and basolateral amygdaloid nucleus (BLAN), the anterior part of the ventral hippocampus (VHPC) and, for control, in the parietal cortex of immature female rats at 21, 26, 32, or 36 days of age, or at the onset of puberty. The cortical cell nuclei did not show any variation of their volumes during the period of development under investigation. In all limbic regions studied, a significant increase of cell nuclear size was found from day 21 to day 26 indicating that a general maturation process runs off in the limbic system during the fourth week of life. Cell nuclei were significantly smaller in 32-day-old rats as compared to 26-day-old females in the MAN, CAN and VHPC, but not in the BLAN. From day 32 to day 36, nuclear volumes had distinctively increased in the MAN and BLAN, not changed in the CAN, and further decreased in the VHPC. The first ovulatory oestrus was associated with diminution of nuclear sizes in the MAN and BLAN, and with enlargement of cell nuclei in the CAN and VHPC. The results which suggest a specific development of different limbic nuclei are discussed with regard to recent findings on the gonadotrophin-controlling function of the limbic system in immature and cyclic female rats.

Aging

[Karyovolumetric studies of postnatal differentiation of the amygdaloid complex in ovarectomized rats].

The caryovolumetrically definable prepubertal morphokinesis of the medial, cortical and basolateral amygdaloid nuclei in intact female rats (DOCKE and SMOLLICH 1978), which is probably related to the maturation of the ovulatory meachnisms, could not be demonstrated in females ovariectomized on the first day after birth and autopsied at 21, 26, 32, 36 or 39 days of age. Simultaneously, postnatal castration induced a specific stimulation of the metabolic activity of amygdaloid neurons. A distinct increase of cell nuclear volumes as compared to intact rats was recorded in the medial and basolateral amygdaloid nuclei and, to a lower degree, in the cortical amygdaloid nucleus. Neurons located in the parietal cortex did not respond in this way. The findings support the assumption that the mediocortical and basolateral amygdaloid regions belong to the cerebro-hypophyseo-gonadal axis and are involved in the differentiation and/or maturation of this axis.

Aging

[Regulation of the endocrine system].

The universal significance of the endocrine system for the regulation of the vital functions and the extra ordinarily high biological activity of the hormones require sensitive mechanisms of regulation within this system. The central nervous system is integrated into these regulatory processes and controls by neurotransmitters and hypothalamic releasing and inhibiting of the hormones the secretion of the hypophyseal and peripheral hormones. Central and peripheral feed-back mechanisms making possible the adaptation of the neuroendocrine system to changing external and internal conditions are operative between the peripheral endocrine glands and the hypothalamo-hypophyseal system as well as during synthesis, transport, action and metabolism of hormones. The knowledge of the fundamental regulatory mechanisms is a presupposition for the effective diagnosis and therapy of endocrine dysfunctions.

Endocrine Glands

[Relationship between the limbic system and gonadal function. 2. Quantifiable prepuberal differentiation of medial cortical amygdaloid nuclei].

In juvenile female rats beteen the 21st and 26th days of age, the neurons of the medial and cortical amygdaloid nuclei undergo a highly significant karyovolumetrically measurable activation which, however, partially declines almost immediately. Such prepuberal variation of activity was found to be correlated with age-dependent effects of direct interventions with these nuclear regions upon the hypothalamy-pituitary-gonadal axis, e.g. implantation of oestradiol benzoate, stimulation or lesioning. This basically, is a quantitatibe-morphological confirmation of an assumption that had been derived earlier from experimental studies, according to which the mediocortical part of the amygdala undergoes in the prepuberal period a functional muteration or differentiation which is specific and related to puberty and gonadal functions (Döcke, 1976a, b; Döcke et al., 1976).

Aging

Different effects of amygdaloid lesions on compensatory ovarian hypertrophy in cyclic and prepubertal female rats.

Cyclic and 28-day-old immature female rats were hemiovariectomized and partly bilaterally lesioned in the cortical amygdaloid nucleus (CAN). The compensatory ovarian hypertrophy (COH) recorded in the adult females on the 8th day after hemicastration was completely prevented by the amygdaloid lesions. In contrast, damage to the CAN did not alter the ovarian weight in prepubertal females, although COH was also induced in these animals by unilateral ovariectomy.

Amygdala

[Karyovolumetric studies on possible central-nervous-system action sites of the positive estrogen feedback].

In adult, progesterone-pretreated female rats, the medial preoptic and ventral premamillary nuclei of the hypothalamus, and the medial amygdaloid nucleus of the limbic system exhibit a significant karyovolumetrically measurable activation of their neurons after the subcutaneous administration of an ovulation-inducing dose of oestradiol benzoate. The finding suggests that these nuclear regions are sites of action of the positive oestrogen feedback and are involved in the induction of ovulation. The infundibular and lateral septal nuclei, and the bed nucleus of the stria terminalis were also investigated karyovoumetrically but failed to reveal, at the time of testing, any quantifiable morphokinesis that might have been attributable to the administration of the hormone.

Animals

A possible mechanism of the puberty-delaying effect of hippocampal lesions in female rats.

Untreated female Wister rats and females in which advancement of the onset of puberty was induced by bilateral lesioning of the medial preoptic area or the ventromedial-arcuate region, or by the daily s.c. injection of 0.05 microgram oestradiol benzoate/100 g b.w., were bilaterally lesioned in the anterior part of the ventral hippocampus at 21 days of age. Irrespective of the applied treatment, a significant delay of vaginal opening and of the first puberal ovulation resulted from the hippocampal lesions. This delay of the onset of puberty was consistently associated with a retardation of the body weight increase, so that the stage of body development necessary for the occurrence of spontaneous or precocious puberty was reached at later ages in these rats. The results suggest that a normal function of the hippocampus may be necessary for adequate somatic development during sexual maturation.

Animals

Maturation of the oestrogen-dependent LH-stimulating activity of the mediocortical amygdala in female rats.

Immature female Wistar rats were unilaterally implanted with oestradiol benzoate (OB) into the anterior (AMAN) or posterior part (PMAN) of the medial amygdaloid nucleus, or into the central part of the cortical amygdaloid nucleus (CCAN) at different ages. Autopsy was performed 56h after implantation, and the LH concentration in the plasma was estimated by radioimmunoassay. A significant rise of the LH level resulted from implantation of OB: into the PMAN at 21, 26 and 32 days of age, into the AMAN at 32 and into the CCAN at 26 and 36, but not at 32 days of age. The conclusion was drawn that the medial amygdaloid nucleus may be involved in the maturation of the positive oestrogen feedback mechanism. The prepuberal change in the oestrogen-dependent LH-controlling activity of the cortical amygdaloid nucleus indicates that this nucleus may participate in the control of the onset of puberty.

Amygdala