Biomedical subjects

K Köves

Publications and source records attributed to K Köves.

At least 37 records · Page 2Linked to original sources

PubMed1996

New aspects of the neuroendocrine role of PACAP.

The presence of PACAP was revealed in the anterior pituitary with RIA, HPLC, and with the demonstration of its mRNA. The level of PACAP mRNA in the anterior pituitary is the highest during the proestrous LH surge. In our immunohistochemical studies we were able to demonstrate PACAP immunoreactive cells in the anterior pituitary. The shape and the distribution of PACAP immunoreactive cells were very similar to that of the gonadotropes; however, the number of PACAP cells was less than that of LH cells. Additionally, another PACAP-positive cell population with small diameter appeared in the proestrous stage, during pregnancy and lactation. Double labeling revealed that the major part of large PACAP cells exhibited LH immunoreactivity and those with a small diameter contained PRL. It is not clear whether the pituitary- or the hypothalamic-born PACAP, or both, influence pituitary LH and PRL secretion. I.c.v. administration of PACAP just prior to the critical period in the proestrous stage inhibited the expected ovulation and blocked the proestrus LH and PRL surge, although i.v. administration of PACAP had no effect. PACAP antiserum did not interfere with ovulation when i.c.v. or i.v. injection was used. Our results support the view that PACAP has a role in the control of LH and PRL secretion during the estrous cycle, pregnancy, and lactation. The inhibitory effect of PACAP on ovulation is mediated through the hypothalamus.

Animals↗

PubMed1996

PACAP participates in the regulation of the hormonal events preceeding the ovulation.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a member of the secretin family. It was isolated and characterized in 1989. Its neuroendocrine role was demonstrated in vivo and in vitro systems. It seems that in vivo the effect of PACAP on the gonadotrop hormone secretion depends on the route of administration. It was reported that intravenous (i.v.) injection of PACAP elevated, while intra-cerebro-ventricular (i.c.v.) administration depressed plasma LH levels. In the present study it was demonstrated that PACAP, administered i.c.v. before the critical period of the proestrous stage, blocked the ovulation and prevented the proestrous LH surge in rats. The blocking effect of PACAP is not directly mediated by endogenous opioids because the antagonizing effect of Naloxone, an opioid receptor antagonist, was questionable. Under our experimental conditions we could not confirm the stimulating effect of i.v. administered PACAP.

Animals↗

PubMed1994

Present status of knowledge about the distribution and colocalization of PACAP in the forebrain.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a recently discovered member of the secretion family. 1. PACAP is a well conserved peptide during the phylogenesis. It has two bioactive amidated forms: PACAP38 and PACAP27 with 38 and 27 residues, respectively. 2. PACAP and its receptors are widely distributed in the central and peripheral nervous systems and in non-neural tissues. 3. In the central nervous system PACAP immunoreactive neuronal elements have been observed in the hypothalamus (magno- and parvocellular cell groups), both layers of the median eminence, the septum, the thalamus, the amygdaloid complex, the hippocampus, and various regions of the cortex. 4. In the periphery, PACAP was found in small sensory and parasympathetic neurons. 5. In the hypothalamus PACAP partially colocalizes with oxytocin- and tyrosine hydroxylase-immunoreactivities. In the septum there is no colocalization between the two immunoreactivities, but PACAP- and tyrosine hydroxylase-immunoreactive fibers were often found to establish synaptic contacts with the same, unlabeled dendrite. It was reported that in the periphery, in sensory neurons PACAP colocalized with substance-P and in parasympathetic neurons with acetylcholin. 6. PACAP functions as a neurotransmitter, hypothalamic releasing factor, posterior pituitary hormone, and trophic factor of the nervous tissue. PACAP also participates in neuro-immunoendocrine mechanisms.

Animals↗

PubMed1992

Pituitary adenylate cyclase activating peptide: a novel vasoactive intestinal peptide-like neuropeptide in the gut.

Pituitary adenylate cyclase activating peptide (PACAP) is a vasoactive intestinal peptide (VIP)-like hypothalamic peptide occurring in two forms, PACAP-27 and the C-terminally extended PACAP-38. The predicted rat and human PACAP sequence is identical to the isolated ovine one. In the present study, the occurrence and distribution of PACAP-like peptides were examined in the gut of several species by immunocytochemistry and immunochemistry using an antibody raised against PACAP-27. PACAP-like immunoreactivity was observed in nerve fibers in the gut wall of all species examined (chicken, mouse, rat, hamster, guinea-pig, ferret, cat, pig, sheep and man). In the chicken and human gut, immunoreactive fibers were numerous in all layers. In the other species examined the fibers were predominantly found in the myenteric ganglia and smooth muscle. Delicate PACAP-immunoreactive fibers were seen in the gastric mucosa of mouse, rat, hamster and man but not in the other species examined. The chicken proventriculus harbored numerous PACAP-immunoreactive endocrine cells which were identical with the serotonin-containing cells storing gastrin-releasing peptide. PACAP-immunoreactive nerve cell bodies were numerous in the submucous ganglia and moderate in number in the myenteric ganglia of the human gut. They were few in the intramural ganglia of the other species examined. Extrinsic denervation (performed on segments of rat and guinea-pig small intestine) did not visibly affect the PACAP innervation, indicating an intramural origin of most PACAP-immunoreactive fibers. Double immunostaining for VIP and PACAP revealed co-existence of the two peptides in nerve cell bodies and nerve fibers of the human and chicken gut and in fibers in the gastric mucosa of mouse and rat. In all other species examined and in all other locations in the gut PACAP-immunoreactive nerve cell bodies and nerve fibers were distinct from those storing VIP; many of them contained gastrin-releasing peptide instead. Immunochemistry revealed PACAP-like peptides in gut extracts of all species studied; upon high performance liquid chromatography the immunoreactive material co-eluted with synthetic PACAP-27. The distribution of PACAP-immunoreactive nerve cell bodies and nerve fibers in the gut wall suggests their involvement in the regulation of both motor and secretory activities.

Amino Acid Sequence↗

PubMed1991

Comparative distribution of immunoreactive pituitary adenylate cyclase activating polypeptide and vasoactive intestinal polypeptide in rat forebrain.

Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are structurally similar, share the same high affinity site in same peripheral tissues and increase the intracellular content of adenylate cyclase. To establish which neural circuits are signaling with each of these two peptides, we systematically compared the immunohistochemical distribution of PACAP and VIP in selected rat forebrain regions using previously characterized antiserum. The PACAP antiserum recognized both PACAP27 and PACAP38, and PACAP immunoreactivity was unaffected by preincubation with various other peptides. PACAP-immunoreactive perikarya and fibers were observed in both hypothalamic and extrahypothalamic regions. In the hypothalamus PACAP perikarya were located in the supraoptic, paraventricular, anterior commissural, periventricular, and perifornical nuclei. In intact rats PACAP immunolabeled fibers were present in the internal zone of the median eminence and posterior pituitary. One week after hypophysectomy the intensity of staining in the internal zone was enhanced and immunoreactive fibers appeared in the external zone of the median eminence. Two or 3 weeks later a dense fiber network was observed around the portal capillaries in the external zone, and immunoreactive material further accumulated in the fibers of the internal zone. PACAP-immunoreactive perikarya and fibers were also observed in several extrahypothalamic regions including central thalamic nuclei, amygdaloid complex, bed nucleus of stria terminalis, septum, hippocampus and cingulate, and entorhinal cortices. In the lateral septum and entorhinal cortex PACAP fibers surrounded unstained neuronal cell bodies and small blood vessels. In intact rats, VIP-immunoreactive perikarya were present in all regions of the cerebral cortex, hippocampus, amygdaloid complexus and in the suprachiasmatic nucleus, but not in the paraventricular and supraoptic nuclei. In colchicine-treated rats the VIP perikarya appeared in the preoptic area and paraventricular nucleus. The fibers were organized in two main pathways: the stria terminalis and an ascending pathway from the suprachiasmatic nucleus to the paraventricular area. Hypophysectomy induced the appearance of VIP-immunoreactive fibers in the internal zone of the median eminence and perikarya in the supraoptic and paraventricular nuclei in addition to the suprachiasmatic nucleus. The dissimilar distributions of PACAP and VIP suggest that PACAP neural circuits are independent of that of VIP in the rat forebrain. These findings support possible multifunctional roles for PACAP as a posterior pituitary hormone, a hypophysiotrophic factor, and a neurotransmitter/neuromodulator.

Amygdala↗

PubMed1990

Demonstration of specific binding sites for pituitary adenylate cyclase activating polypeptide (PACAP) in rat astrocytes.

The high and low affinity binding sites for PACAP were identified in rat astrocytes using [125I]PACAP27 as the labeled ligand. Scatchard analysis of displacement of the bound tracer by unlabeled PACAP27 indicated the existence of two classes of binding sites, with the dissociation constant (Kd) = 1.22 +/- 0.4 nM, the binding maximal capacity (Bmax) = 821 +/- 218 fmols/mg protein for the high affinity binding site, and Kd = 0.59 +/- 0.06 microM, Bmax = 563 +/- 12 pmols/mg protein for the low affinity binding site, respectively. The specificity of [125I]PACAP27 binding was tested using PACAP38 and peptides structurally related to PACAP, such as VIP, GHRF, PHI, secretin and glucagon. PACAP38 completely displaced the binding of [125I]PACAP27 and Scatchard analysis also indicated the presence of two classes of binding sites with similar Kd and Bmax to those for PACAP27. VIP and GHRF competed with [125I]PACAP27, but to a much lesser extent than unlabeled PACAP27 in binding. Other peptides tested did not displace the binding of [125I]PACAP27 at 10(-6) M.

Analysis of Variance↗

PubMed1990

Presence of immunoreactive vasoactive intestinal polypeptide in anterior pituitary of normal male and long term estrogen-treated female rats: a light microscopic immunohistochemical study.

The presence and synthesis of vasoactive intestinal polypeptide (VIP) has been demonstrated in the rat anterior pituitary. It was recently confirmed that immunoreactive VIP is present in the anterior pituitary, and in a thyroid-deficient state, VIP could be detected by light microscopic immunohistochemistry. It has also been suggested that VIP plays a stimulatory role in PRL secretion. To gain more detailed information on the localization of VIP and the conditions that alter the synthesis of VIP, we examined VIP immunoreactivity using immunohistochemistry in pituitaries of normal male and cycling female rats and in those states in which PRL secretion was enhanced (pregnancy, lactation, long term estrogen treatment, and pituitary implanted under kidney capsule of normal or estrogen-treated female rats). In situ, implanted and cultured pituitary cells were stained for VIP immunoreactivity using the peroxidase-antiperoxidase method. VIP immunoreactivity was observed in about 45% of the male rats, in all estrogen-treated female rats, in the implanted pituitaries under the kidney capsule (three of five from estrogen-treated and one of five from intact females, respectively), and in the pituitary cell cultures derived from estrogen-treated rats. Using a double labeling procedure we have also observed PRL immunoreactivity in a small population of the VIP-positive cells. These results suggest a positive regulatory role of estrogen in expression of the VIP gene. The physiological and pathophysiological significance of VIP in PRL secretion, however, remains to be clarified.

Animals↗

PubMed1990

Immunohistochemical demonstration of a novel hypothalamic peptide, pituitary adenylate cyclase-activating polypeptide, in the ovine hypothalamus.

We recently reported isolation, characterization and synthesis of a novel ovine hypothalamic peptide with 38 residues which stimulates accumulation of cAMP in rat anterior pituitary cell cultures. The peptide was named PACAP38 (pituitary adenylate cyclase-activating polypeptide with 38 residues). The presence of another peptide corresponding to the N-terminal 1-27 residues (PACAP27) was also demonstrated. Both PACAP38 and PACAP27 have an amidated C-terminus. Antisera against synthetic PACAP27 were generated in rabbits. These antisera were tested for titer and specificity in enzyme-linked immunosorbent assay. One of the antisera (no. 88121-3) exhibited a high titer of antibody, which was specific to PACAP27 and PACAP38 with exception of slight cross-reactivity with ovine CRF (oCRF). Therefore, the antibodies against oCRF were removed from the antiserum using a solid phase method. Removal of oCRF antibodies was confirmed by enzyme-linked immunosorbent assay. A dense immunoreactive fiber network was found in both external and internal zones of the median eminence and pituitary stalk. The fibers were demonstrated to be in close contact with the hypophysial portal capillaries. The preabsorption of antiserum with vasoactive intestinal polypeptide or with the mixture containing TRH, LHRH, oCRF, ovine GH-releasing factor, somatostatin, and bovine thyroglobulin did not affect the immunostaining. On the other hand, the preabsorption of antiserum with an excess of PACAP27 or PACAP38 abolished the immunostaining. Therefore, the staining is considered specific for PACAP27 and PACAP38. Stained fibers were also present in the posterior pituitary. A dense fiber network was observed and the lateral hypothalamus the fibers appeared to cling to unstained neuronal cell bodies and their dendrites. In the lateral septum the fibers surrounded some blood vessels. Immunolabeled cell bodies were found in the paraventricular and supraoptic nuclei. These findings support the view that PACAP may play a multifunctional role, including that of a hypophysiotropic hormone, neurotransmitter, neuromodulator, and vasoregulator.

Amino Acid Sequence↗

PubMed1989

Gonadotropin-releasing hormone binding sites in ovaries of normal cycling and persistent-estrus rats.

The gonadotropin-releasing hormone (GnRH) binding capacity in ovaries and pituitaries of normal cycling rats at different stages of the estrous cycle and in ovaries of persistent-estrus rats was measured using radioligand-receptor assay (RRA). Persistent estrus was induced either by neonatal administration of testosterone propionate (1.25 mg s.c.) on the second day of life or by a hypothalamic suprachiasmatic frontal cut made with Halász' knife. All animals were killed during the critical period (1400-1600 h), and GnRH receptor was assayed. GnRH receptor levels in both ovaries and pituitaries changed during the estrous cycle. The total number of ovarian GnRH binding sites was significantly higher in proestrus than in diestrus 1, the stage in which the lowest level was found. When binding sites were expressed in fmol/mg ovary, the highest level was observed in diestrus 2; however, no changes were observed during the estrous cycle when GnRH binding sites were expressed as fmol/mg protein. Changes noted were very similar to those demonstrated in pituitary GnRH receptors in our present and previous experiments. Higher levels of pituitary binding sites were found in diestrus 2 and proestrus than in estrus and diestrus 1. The changes in the GnRH receptor levels were more striking in the pituitary than in the ovaries. It appears that the total number of ovarian GnRH binding sites was not altered in either of the two persistent-estrus groups, but that their concentration was significantly higher (expressed in fmol/mg ovary or fmol/mg protein) than on any day during the estrous cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Solid-phase adsorption method for removing undesired antibodies from polyclonal antiserum.

We have developed a novel and simple method, requiring only a small amount of antigen, for removal of undesired antibodies from antiserum. The method was established using a well-characterized antiserum against rat luteinizing hormone (anti-rLH). Wells of polystyrene tissue culture plates were coated with rat LH (rLH). Anti-rLH diluted 1:3000 was added to rLH-coated wells and shaken to remove LH antibodies. Control anti-rLH was treated in a similar manner in non-rLH-coated wells. Both antisera were tested by immunocytochemistry on rat pituitaries. Antiserum from rLH-coated wells stained no cells, whereas the control serum stained cells that were morphologically typical of LH cells. The effectiveness of this antibody removal was also confirmed in a modified ELISA. In another experiment, anti-rLH and anti-hTSH beta sera were mixed. The final dilution of both antisera was 1:10,000. Anti-rLH was removed by the purification method described. Completeness of antibody removal was confirmed by a double-immunohistochemical staining of rat pituitary in which sections were first stained by the PAP method and then stained with an immunofluorescence procedure after elution of the first antigen-antibody complex. The mixed antiserum incubated in rLH-coated wells did not stain LH cells. There was no co-localization between the LH immunopositivity demonstrated by an anti-rLH serum using immunofluorescence and cells immunostained with the purified antiserum using the PAP method. As indicated in ELISA, the titer of the TSH beta antiserum was not decreased compared to that of the untreated, mixed control antiserum, and the LH antibodies were eliminated by the treatment. This new purification method has four distinct advantages: (a) antiserum is not treated chemically; (b) it requires only a small amount of antigen compared with the amount required for affinity chromatography; (c) neither the undesired antigen-antibody complex(es) nor an excess amount of antigen is present in the purified antiserum; and (d) removal of undesired antibodies can be monitored by ELISA.

Adsorption↗

PubMed1989

Transitory increase in plasma FSH and LH levels induces early vaginal opening and corpus luteum formation in ovarian transplants of rats ovariectomized at 20 days of age.

The effect of a transitory increase in plasma FSH and LH levels on puberty has been investigated. Hormonal changes were induced by bilateral ovariectomy (OVX) at 20 days of age followed by implantation of two ovaries (donor animals 20-day-old) beneath the kidney capsule 1, 2 or 3 days later. In an other group of animals the two interventions were made in reversed order. Rats in which OVX was made first showed early vaginal opening. If ovarian implantation preceded OVX, these two interventions did not affect the time of vaginal opening. More than 1/3 of the ovarian implanted animals exhibiting early opening of the vagina contained corpora lutea three days after vaginal opening. FSH and LH levels of OVX + ovary implanted rats were from the third day on following implantations markedly different from the OVX controls and were in the range of intact or sham-operated rats. The present findings indicate that a transitory increase in plasma gonadotropin levels around twenty days of age may lead to precocious puberty.

Age Factors↗

PubMed1988

Hypothalamus and puberty.

The effect of a transitory increase in plasma FSH and LH levels during the prepubertal period on puberty has been investigated. Twenty-day-old rats had been bilaterally ovariectomized and 24 hr later they received two ovaries of infantile rats beneath the kidney capsule. These rats exhibited precocious puberty. Animals into which two additional ovaries had been transplanted first and the next day their own ovaries removed showed puberty at the same time as controls. Additional investigations provided evidence that the ovariectomized and ovary implanted rats plasma FSH and LH levels were in the control range four days after implantation. The findings support the assumption that the hypothalamic lesion-induced precocious puberty is due rather to a transitory enhanced release of gonadotropin releasing hormone by the lesion than to the destruction of sex-steroid sensitive structures inhibiting the release of gonadotropic hormones in prepubertal rats.

Animals↗

PubMed1988

Neural control of ovulation.

Pituitary gonadotrophin function is controlled to a great extent by the central nervous system and by the feedback action (positive and negative) of sex steroids. Neural structures involved in this mechanism may be divided into two levels. The first level is represented by the nervous structures releasing gonadotrophin-releasing hormone (GnRH) in a pulsatile manner into the portal circulation. The gene encoding the precursor protein for GnRH has been described recently. The precursor protein appears to be composed of 92 amino acids, in which the GnRH decapeptide is preceded by a signal peptide and followed by a peptide termed GAP for GnRH-associated peptide. The GnRH-synthesizing neurones and the nervous structures synchronizing the GnRH discharge (pulse generator) in the monkey, and probably also in the human, reside in the medial basal hypothalamus, which appears to have a highly integrated structure. The GnRH pulse generator is influenced by nervous structures outside the medial basal hypothalamus (second level of control) as well as by ovarian and other hormones. These influences probably impinge directly or indirectly on the hypothalamic oscillator. Concerning the chemical nature of the substances mediating the action, a large number of neurotransmitters and neuropeptides have been reported to influence GnRH secretion.

Animals↗

PubMed1988

Pituitary gonadotropin-releasing hormone binding sites in persistent estrous rats.

Pituitary gonadotropin-releasing hormone (GnRH) binding sites were studied in persistent estrous rats. For comparison females at different stages of the estrous cycle, ovariectomized animals, and intact males were examined. Persistent estrus was induced by a hypothalamic knife cut, administering testosterone to neonatal rats, or by constant illumination. Rats showing spontaneously such alteration were also used in the experiment. Besides pituitary GnRH-binding sites, the GnRH content of the median eminence and plasma luteinizing hormone, follicle-stimulating hormone, estradiol, and progesterone concentrations were determined. Pituitary GnRH receptors changed during the estrous cycle with the highest concentrations observed on proestrus. In rats in persistent estrus, pituitary GnRH-binding sites varied between proestrous and estrous values of cyclic females. Ovariectomy resulted in a significant increase in receptors. Depending on how the persistent estrous syndrome was induced, very different amounts of GnRH were found in the median eminence of the various groups. Our data indicate that the GnRH-binding sites on pituitary cells of persistent estrous rats are in essence not changed.

Animals↗

PubMed1986

Effect of various hypothalamic deafferentations injuring different parts of the GnRH pathway on ovulation, GnRH content of the median eminence, and plasma LH and FSH levels.

Various supra- and retrochiasmatic cuts injuring different parts of the septo-preoptico-infundibular GnRH pathway were made in adult female rats, and their effects on ovulation, median eminence (ME) GnRH content and on plasma LH and FSH levels were studied. Extended retrochiasmatic frontal cut just behind the optic chiasm, or a frontal cut in front of the suprachiasmatic nucleus presumably interrupting the whole GnRH pathway blocked ovulation, led to persistent estrus with polyfollicular ovaries, and reduced the ME GnRH content to 10 and 32%, respectively, expressed in percentage of unoperated control value. Severance of the GnRH pathway on one side or partial interruption of the pathway on the two sides in the retrochiasmatic area did not interfere with ovulation, and the ME GnRH content was 50% or more of the control value. Disconnection of the GnRH fibers coming from the septum resulted in a more than 30% decrease in the GnRH content of the ME, but did not block ovulation. Two separate symmetrical lateral cuts in the suprachiasmatic area leaving intact the presently known GnRH pathway reduced the ME GnRH content to 40% of the intact value, but did not interfere with ovulation. Plasma LH and FSH levels of the animals with different knife cuts were considerably dissociated and there were no apparent correlations between brain interventions and the concentrations of these two hormones in the blood. Our previous findings together with the present data suggest that: half of the GnRH pathway, medial or lateral bundles of the pathway on the two sides are sufficient for ovulation and cyclic gonadotrophic function; persistent estrus develops if the ME GnRH content is below 40% of the control value, and about 60% of the ME GnRH originates outside the preoptic, supra- and retrochiasmatic region. Half of this 60% may come from the septum and the vertical part of the diagonal band of Broca, the other half from the region in front of the preoptic area. The remaining 40% presumably arises from the preoptic (7-10%), supra- (15-20%) and retrochiasmatic region (8-10%).

Animals↗

PubMed1986

Axonal regeneration following retrochiasmatic deafferentation in young and adult rats.

Regeneration of nerve fibres after hypothalamic knife cuts was studied by the anterograde transport of horseradish peroxidase [HRP] in female rats of various ages. Retrochiasmatic frontal cuts were made in 2, 5, 7 and 11-day-old and in adult rats. Four, 6, 7 and 12 months later HRP was injected rostral to the cut-line in the suprachiasmatic area. HRP-stained nerve fibres ran rostro-caudally from the injection site through the cut-line in animals operated upon at 2, 5 and 7 days of age. In contrast to the former group, animals operated on the 11th day of life as well as in adult rats no HRP-stained nerve fibres could be seen passing through the cut-line which was marked by scar formation. In one animal operated in adulthood a bundle of nerve fibres noticed 7 months after the surgery turned medially at the caudal end of the cut-line and spread over the frontally deafferented area. The character of these newly formed fibres was different: part of them showed a varicose appearance, the others exhibited even contours. The present findings indicate that the deafferented [or isolated] hypothalamus remains neuronally isolated from the environment if the operation is carried out later than the end of the first week of life. Operations made during the first postnatal week do not leave permanent traits in the brain.

Afferent Pathways↗

PubMed1986

Further data on the origin of gonadotropin releasing hormone in the median eminence of the rat hypothalamus.

Gonadotropin releasing hormone (GnRH) content of the two halves of the median eminence of the rat hypothalamus was determined by radioimmunoassay three weeks after three different unilateral knife cuts around the preoptic area. A unilateral cut in front or above the area caused a more than 25% decrease in the GnRH content of the two halves of the median eminence. A cut lateral to the preoptic region had only a slight effect similar to that observed after sham operations. The data suggest that probably more than 50% of the rat median eminence GnRH derives from outside the preoptic-suprachiasmatic region. The GnRH fibres projecting to the median eminence but arising from outside the preoptic region, probably mainly from GnRH perikarya in the limbs of the diagonal band of Broca and septum, enter this area partly from rostral and partly from above, but not from lateral direction. partly from rostral and partly from above, but not from lateral direction. Several of these fibres probably cross before terminating in the median eminence.

Animals↗

PubMed1986

Data suggesting that milk of early lactation period might be involved in sexual differentiation of rat brain.

The contribution of a hypothetic milk factor in the masculinization process of gonadotropin secretion pattern was investigated using a cross-fostering model. Adult female rats whose nipples had been previously excised were mated. At the time of delivery their pups were given to recipient dams that had given birth one week earlier. Pups remaining with their own (intact) mother served as control group. At the age of 37-39 days (birth = day 0) male rats from the experimental and the control groups were castrated and also control females were ovariectomized. Ten days later gonadectomized animals received ovarian grafts excised from 20-day-old rats. Four and seven days after transplantation the grafts were processed for histology. Corpus luteum formation suggests that male rats nursed by recipient dams did not undergo the masculinization process normally occurring during the first few days of postnatal life. In a separate experiment, male pups nursed by dams being at the early lactation (control) or at the midlactation period were decapitated on postpartum day 1 and serum testosterone levels were measured by RIA. Mean testosterone concentration was almost twice as high in the control group than in pups nursed by recipient dams of the midlactation period. These data suggest that milk of the early lactation period might be necessary for the normal masculinization process of the male rat.

Animals↗