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S R Ojeda

Publications and source records attributed to S R Ojeda.

At least 145 records · Page 8Linked to original sources
PubMed1982

Pulsatile luteinizing hormone (LH) patterns in ovariectomized rats: involvement of norepinephrine and dopamine in the release of LH-releasing hormone and LH.

Cannulated ovariectomized (OVX) rats were bled every 10 min for 2 h to characterize their individual patterns of LH release. After the last sample, all rats were decapitated, and their brains were removed for analysis of LHRH, norepinephrine (NE), and dopamine (DA) levels in median eminence (ME), arcuate-ventromedial, and suprachiasmatic-medial preoptic region (Sch-PO) to determine if changes in NE, DA, and LHRH levels in any of those areas could be observed at different points during the pulsatile release of LH. The results showed that when LH levels started to increase, NE levels peaked in the Sch-PO, whereas a sharp drop in DA and LHRH levels in the ME was detected, which may reflect an acute release in the ME of both DA and LHRH. When LH levels reached peak values, NE levels in the Sch-PO returned to lower values, and DA and LHRH in the ME rose to higher levels. Inhibition of NE synthesis with diethyldithiocarbamate resulted in the suppression of LH pulses. L-Dopa administered after diethyldithiocarbamate induced an increased release of LH in both OVX and OVX, estrogen-primed rats with a simultaneous inhibition of PRL release. Peak levels of LH after L-dopa treatment coincided with increased DA levels in the ME, no change in NE, and a clear drop in LHRH. The results suggest that both NE and DA are involved in the pulsatile release of LH in OVX rats.

Animals↗
PubMed1981

TSH release during the estrous cycle of the rat: variations in responsiveness to cervicovaginal stimulation.

Serum TSH, LH and FSH were measured at various times during the day, during the estrous cycle of the rat. Proestrous surges of FSH and LH were detected as previously reported. TSH values fell to low levels in the late afternoon on each day of the cycle. There was a significant elevation of TSH at 13.00 h on both proestrus and estrus. The elevation of TSH on proestrus was accompanied by a significant fall in pituitary TSH stores. LH stores were also significantly depleted by 19.00 h on proestrus. Cervicovaginal stimulation by a glass rod provoked a significant rise in serum TSH 3 h after stimulation at 10.00 h on estrus but not on other days of the cycle. Responsiveness to a test dose of TRH varied during the cycle. It was maximal on proestrus and declined to minimum values on diestrus day II. Values were further lowered after ovariectomy but were restored to diestrus day II levels by treatment with estradiol. It is concluded that there are important cyclic variations in TSH release in the female rat, that cervicovaginal stimulation can provoke TSH release on estrus and that these changes are associated with altered responsiveness to TRH. We conclude that ovarian steroids modulate the release of TSH from the pituitary and affect the responsiveness to cervicovaginal stimulation. These changes are presumably brought about by alterations in TRH release and in responsiveness of the pituitary to the neurohormone.

Animals↗
PubMed1981

Changes in ovarian LHRH receptor content during the onset of puberty in the female rat.

LHRH and some of its analogs have been reported to exert inhibitory effects on ovarian function, seemingly following interaction of the neurohormone with specific, high affinity binding sites. The present experiments were undertaken to determine whether LHRH binding sites in the ovary undergo quantitative changes during the onset of puberty in the rat. Changes in LHRH receptor content were assessed by the binding of the stable LHRH analog, [D-Ala6, Pro9]-LHRH to ovarian membrane preparations. LHRH binding in prepubertal rats (anestrus, A) was 166 +/- 11 fmol/mg protein, declined gradually (to 127 +/- 14 fmol/mg protein) during the early proestrous (EP) phase of puberty--a time at which intrauterine fluid begins to accumulate and uterine weight increases more rapidly--and became even lower (75 +/- 4 fmol/mg protein) by 1300 h of the day of first proestrus (LP), prior to the initiation of the first gonadotropin surge. At the time of the surge (1600 h) binding was 70 +/- 3 fmol/mg protein. LHRH binding was minimal on the day of the first estrus (E) and increased slightly on diestrus (D). The results indicate that the ovarian steroidogenic activation that precedes the first surge of gonadotrophins in the rat is associated with a marked loss in ovarian LHRH receptor content and suggest that a reduction in LHRH inhibitory function within the ovary may be a contributing factor to the pubertal enhancement in ovarian secretory activity.

Animals↗
PubMed1981

A quantitative analysis of the maturation of steroid negative feedbacks controlling gonadotropin release in the female rat: the infantile-juvenile periods, transition from an androgenic to a predominantly estrogenic control.

To determine what ovarian or adrenal steroid(s) are involved in restraining gonadotropin secretion in infantile female rats, several experiments were performed. Adrenalectomy of 10-day-old rats markedly decreased serum progesterone (P) and, to a lesser extent, serum estradiol (E2) levels. Androgen (A) levels were only transiently reduced, and serum dihydrotestosterone was not affected. Serum LH and FSH, on the other hand, increased only transiently after adrenalectomy. Ovariectomy (OVX) failed to decrease serum P and partially depressed serum E2, but resulted in a marked fall of both testosterone (T) and dihydrotestosterone. Serum LH and FSH were increased in these animals. Replacement of pre-OVX serum T levels via Silastic capsules prevented the postcastration rise in both LH and FSH, suggesting that the increase in gonadotropins that follows OVX of 10-day-old rats is, to a large extent, a consequence of the loss of ovarian T. OVX of juvenile (27 days old) rats increased serum FSH and LH 48 h later and reduced both serum T and E2 levels, with no significant change in serum P. Replacement of pre-OVX serum T levels depressed post-OVX serum FSH and LH titers only partially. In contrast, replacement of pre-OVX serum E2 levels, effectively suppressed the postcastration rise in serum gonadotropins. The results suggest that 1) during the infantile period, gonadotropin release is predominantly under ovarian androgenic inhibitory control, but this mechanism is not very effective, because basal serum gonadotropin levels, particularly FSH, are elevated; 2) the effectiveness of the A negative feedback on FSH remains unchanged during prepubertal development; and 3) the previously reported increase in E2 negative feedback effectiveness that occurs after day 15 results in an E2 inhibitory signal that surpasses that of As, so that during juvenile days, most of the ovarian steroidal inhibitory control on gonadotropin release is mediated by E2.

Adrenal Glands↗
PubMed1981

Hyperprolactinemia-induced precocious puberty: studies on the mechanism(s) by which prolactin enhances ovarian progesterone responsiveness to gonadotropins in prepubertal rats.

Hyperprolactinemia induced in immature female rats by treatment with sulpiride, a dopaminergic receptor blocker, increased the in vitro release of ovarian progesterone (P) in response to different doses of both highly purified hCG and human FSH. The increased P response to gonadotropins was also observed in ovaries of animals injected with ovine PRL or in rats in which the hyperprolactinemic condition was induced by pimozide, a more typical dopaminergic receptor blocker. In addition, the pimozide treatment advanced the time of puberty in a manner similar to that previously observed with sulpiride. In other experiments in which only the ovarian response to hCG, but not that to FSH, was evaluated, it was found that the in vivo treatment of hypophysectomized immature rats with sulpiride did not modify the almost undetectable serum PRL levels of these animals and failed to increase the in vitro ovarian P response to hCG. By contrast, sc injection of PRL to hypophysectomized rats clearly enhanced the in vitro release of P in response to the gonadotropin. Adrenalectomy of otherwise intact rats significantly decreased the in vitro ovarian P response to hCG and blunted the increase in the P response induced by hyperprolactinemia. These effects, however, were almost completely reversed by concomitant corticosterone replacement therapy. The ovarian content of hCG receptor in normal rats was found to increase during juvenile development (days 22-31). Hyperprolactinemic animals showed a greater ovarian hCG receptor content than age-matched 31-day-old controls. In contrast, the FSH receptor contents were similar in both groups. The increase in hCG receptor content induced by hyperprolactinemia was even more clearly manifested in isolated granulosa cells, but, as in the case of the whole ovaries, the FSH receptor content in these cells remained essentially the same in hyperprolactinemic and control rats. The results indicate that the enhanced ovarian P response to hCG induced by PRL in prepubertal rats is, at least in part, mediated by an increase in the LH receptor content of the granulosa cells of the developing follicle. It also appears that the sensitizing effect of PRL on the prepubertal ovarian P response to gonadotropins is modulated by the adrenal gland through an effect exerted by corticosterone. The mechanisms by which PRL enhances the ovarian P response to FSH do not appear to involve changes in FSH receptors. However, the occurrence of enlarged uteri in hyperprolactinemic rats suggest that the PRL-induced increase in the P response to FSH may be related to the presence of more mature, estrogen-secreting follicles resulting from the hyperprolactinemic condition.

Animals↗
PubMed1981

Activation of growth hormone short loop negative feedback delays puberty in the female rat.

Implantation of GH in the median eminence of the hypothalamus of 23-day-old female rats tonically inhibited serum GH levels throughout prepubertal development (days 23-36) and depressed GH diurnal pulsatile release. Puberty was significantly delayed in GH-deficient animals, a delay associated with a blunted in vitro ovarian steroidal responsiveness to gonadotropins (particularly estradiol) and a marked decrease in prepubertal uterine weight, as evaluated 4, 7, and 13 days after GH implantation. The prepubertal body weight increase was also depressed. Neither ovarian weight nor serum levels of LH, FSH, PRL, or TSH were consistently altered by the GH implant. In addition, evaluation of pulsatile PRL release in 33-day-old rats revealed no difference between control and GH-deficient animals. Ovarian LH receptor content was lower in GH-implanted rats than in controls, suggesting that a decrease in LH receptors may be one of the mechanisms by which a chronic decrease in serum gH depressed the prepubertal ovarian estradiol and, to a lesser extent, the progesterone response to gonadotropins. A direct ovarian site of action for GH was indicated by the results of experiments in which GH was administered to immature hypophysectomized estrogen-treated rats. The in vitro ovarian progesterone response of the GH-treated animals to both hCG and human FSH was distinctly increased by prior in vivo GH treatment. This effect of GH was not reproduced either by the in vivo administration of LH at a dose calculated by RIA to be contaminating the GH preparation or by FSH at a dose that induced a marked increase in aromatase activity in the same ovaries. GH treatment of hypophysectomized rats failed to affect either aromatase activity or hCG-induced estradiol release, indicating that GH does not directly facilitate the production of estradiol by the ovary. The fact that intact rats with GH implants did not actually show a decrease in the ovarian estradiol response to hCG but, rather, failed to show an increased response at the same time as control animals strongly suggests that ovarian maturation was delayed in GH-deficient rats. It is suggested that, in addition to PRL, GH may also play a role in the process of prepubertal reproductive development by enhancing the steroidal response of the ovary to gonadotropins.

Animals↗
PubMed1981

Changes in ovarian luteinizing hormone and follicle-stimulating hormone receptor content and in gonadotropin-induced ornithine decarboxylase activity during prepubertal and pubertal development of the female rat.

Ovarian hCG and FSH receptor content was measured at different postnatal ages (days 4-32), at 4-day intervals, and expressed as counts per min 125I-labeled hormone bound/micrograms DNA. Specific FSH binding was minimal at day 4 and increased to a maximum at day 28, with the greatest rate of increase between day 4 and 16. hCG receptor content increased 6-fold between day 4 and 32, but contrasting with FSH, its greatest rate of increase occurred between day 16 and 28. The effectiveness of in vivo treatment with LH in inducing ovarian ornithine decarboxylase (ODC) activity, measured in 20,000 X g supernatants by the in vitro formation of 14CO2 from labeled ornithine, increased significantly during prepubertal development (days 21-33), paralleling the changes in hCG receptors. Ovarian hCG and FSH receptor content was also measured during the time of puberty. Specific hCG binding increased from anestrus (juvenile 32-day-old animals) to 1300 h of the first proestrus. The levels declined significantly by 1600 h of first proestrus and reached minimal values by the morning of estrus. Specific FSH binding also increased from anestrus to first proestrus, but to a much lesser degree, the levels showing only minor fluctuations during the rest of the cycle. hCG receptors measured in granulosa cells during puberty increased to an even greater extent than in the whole ovary; binding exhibited an 8-fold increase from anestrus to 1300 h of first proestrus and then declined to much lower values on estrus and the first diestrus. The capacity of LH to induce ovarian ODC activity increased markedly between anestrus and first proestrus, declining thereafter, and again paralleled the changes in LH receptor content. Evaluation of the kinetics of binding of hCG and FSH with their respective receptors in ovaries of 28-day-old rats revealed that the binding of hCG reached equilibrium within 4-8 h, whereas the binding of FSH attained equilibrium between 12-24 h. In both cases, however, the labeled hormones were clearly dissociable from their respective receptors by addition of an excess of unlabeled hormone. Moreover, although the ovarian receptor content of both hCG and FSH increased during prepubertal development, the equilibrium association constant of either hormone with its receptor remained unchanged. The results suggest that the infantile increase in FSH receptors may be induced by the high serum FSH levels present at that age and that, as shown by others in hypophysectomized rats, the subsequent increase in hCG receptors is, at least in part, an FSH-dependent phenomenon. The parallel changes in hCG receptors and LH-induced ODC activity during pre- and peripubertal development strongly suggest that an increase in LH binding capacity plays a fundamental role in the process of ovarian growth. It is also suggested that the changes in the steroidogenic ovarian response to hCG previously observed in peripubertal rats are, at least in part, determined by changes in ovarian LH receptor content.

Animals↗
PubMed1981

Delayed puberty induced by chronic suppression of prolactin release in the female rat.

To study the effect of PRL deficiency on the onset of puberty, PRL release was chronically inhibited by treating immature female rats with the dopaminergic receptor agonist, bromoergocriptine (CB-154). The resulting alterations in the time of puberty onset, and in other associated parameters, such as serum levels of pituitary hormones, ovarian responsiveness to gonadotropins and ovarian hCG receptor content were then evaluated. CB-154 was provided in the drinking water from day 22 onward at the concentration of 20 and 100 micrograms/ml. The treatment resulted in almost complete suppression of serum PRL levels throughout the entire period studied (day 22 to first diestrus). In contrast, serum GH, FSH, and LH levels were not depressed. Likewise, pulsatile release of FSH was not affected and only a subtle alteration in pulsatile LH release was apparent. The onset of puberty, as determined by the age at vaginal opening, and at first diestrus after the first estrus and by the presence of corpora lutea at sacrifice (first diestrus), was markedly delayed in the hypoprolactinemic (HPO) rats. This inhibitory effect of CB-154 was completely prevented by concomitant administration of PRL. Ovarian weight was significantly decreased in HPO rats at the three ages studied (27, 32, and 36 days of age). By day 36, 50% of the control animals had already ovulated, as compared with only 9% of the HPO rats. Microscopic examination of ovaries from HPO rats revealed a retarded follicular development. In vitro ovarian progesterone response to hCG studied at day 32 and 36 of age was reduced in the HPO rats. Uterine growth was also depressed in HPO rats, the ovaries of which, when incubated in vitro, failed to show the prepubertal increase in estrogen response to hCG seen in control rats between day 32 ad 36. Aromatase activity, as measured by the in vitro release of estradiol from ovaries incubated in the presence of an excess of androgen substrate, was depressed in HPO rats. hCG receptor content in the ovaries from HPO rats (counts per min [125]hCG bound per micrograms DNA) was also lower than that of control animals at day 32 and 34 but not at day 36. However, at this later time the hCG receptor content per milligram of ovary was still significantly reduced in HPO rats. The results support the view that PRL plays an important role in the process of ovarian development that leads to the onset of puberty in the female rat and that this effect is, at least in part, exerted through a positive influence of PRL on ovarian LH receptor content.

Animals↗
PubMed1981

Development of estradiol-positive feedback on luteinizing hormone release in the female rat: a quantitative study.

Experiments were conducted to study, in a quantitative manner, the development of estradiol (E2)-positive feedback on LH release in the female rat. A Silastic capsule (20 mm in length/100 g BW) containing E2 dissolved in corn oil (400 micrograms/ml) reproduced first proestrous levels of serum E2 when implanted sc in juvenile rats of different ages (days 20-32). When similar capsules were implanted in infantile rats (days 10-18), serum E2, measured 2 days later, was found to be extremely elevated in 12- and 14-day-old rats (4-6 times higher than first proestrous levels), declining thereafter so that in 16- to 20-day-old rats the levels were only 2-fold greater than proestrous values. Serum levels of alpha-fetoprotein decreased markedly between days 12-28, and both normal and implant-produced serum E2 levels paralleled the decline in the protein titers. However, calculation of the total E2 binding capacity of alpha-fetoprotein indicated that in addition to binding to this protein, there are additional factors responsible for the persistence of E2 in the serum of infantile rats. A LH surge could not be induced in 12- or 14-day-old rats by a 48-h E2 pulse, despite the presence of substantial amounts of free E2, which exerted profound negative feedback effects. Between days 16-20, only E2 levels that were at least 2-fold higher than first proestrous values were effective in inducing a LH surge. Between days 22-34, a LH surge was elicited by serum E2 levels very similar to those seen during the first proestrus. By days 26-28, the profile of the LH surge was indistinguishable from that of the first preovulatory surge. Starting on day 26, and in addition to the LH surge elicited by the 48-h E2 pulse, an earlier surge occurred on the next day after E2 implantation. By day 30, the early LH surge became firmly established, and the late surge was no longer apparent. It is suggested that in the female rat, the development of E2-positive feedback comprises four phases: phase I, before day 16, in which the surge mechanism of the LH-releasing system is not developed; phase II, between days 16-20, in which E2 levels twice as high as those of first proestrus are necessary to activate the LH surge mechanism; phase III, which is initiated at the beginning of the juvenile period (approximately days 20-22) and in which the LH surge mechanism responds to E2 levels of preovulatory magnitude; and mechanism responds to E2 levels of preovulatory magnitude; and phase IV, which begins around days 26-28 and in which a 24-h exposure to E2 levels of preovulatory magnitude is sufficient to elicit a LH surge.

Aging↗
PubMed1981

The maturation of estradiol-negative feedback in female rats: evidence that the resetting of the hypothalamic "gonadostat" does not precede the first preovulatory surge of gonadotropins.

Several experiments were performed to study the changes in the negative feedback of estradiol on gonadotropin secretion around the time of puberty in the female rat. Ovariectomy of juvenile, first diestrus, or adult animals elevated FSH and LH levels 2 and/or 4 days later. Estradiol administered via Silastic capsules, at several dose levels, was much more effective in preventing the postcastration rise of gonadotropins in juvenile than in the older animals. A dose of estradiol that inhibited gonadotropin levels in juvenile rats, but not in adult animals, maintained preovariectomy serum estradiol levels more efficiently in the adult rats. Therefore, a more rapid removal of estradiol from the blood stream cannot explain its lower effectiveness in suppressing gonadotropin release in adult rats. Estradiol-negative feedback effectiveness remained maximal until the day of first proestrus and decreased markedly on the next day (first estrus), remaining low thereafter. "Resetting" of the gonadostat to estradiol negative feedback was advanced by inducing precocious puberty by means of hyperprolactinemia, but not by mimicking the periovulatory changes in serum estradiol and progesterone in the absence of an LH surge. Serum progesterone levels were much higher in postpubertal rats than in juvenile animals. Ovariectomy of juvenile rats slightly decreased the already low levels of serum progesterone, but it produced a striking progesterone decrease in postpubertal animals. Quantitative replacement of preovariectomy serum progesterone levels in adult rats, treated with an ineffective dose of estradiol, almost completely restored the prepubertal effectiveness of estradiol in inhibiting LH release and, to a lesser extent, release of FSH...

Animals↗