Anti-estrogenic suppression of the lordosis response in female rats

The anti-estrogen, CI 628, was used to suppress the lordosis response induced by sequential injections of estrogen and progesterone in ovariectomized (OVX) female rats. Appropriate doses of CI 628 completely abolished sexual receptivity in females administered estradiol benzoate (EB) in sesame oil. This behavioral effect could be attenuated by providing increased quantities of EB or decreased quantities of CI 628. Anti-estrogenic effects on lordosis induced by free estradiol in saline (E) were assessed after first establishing behaviorally equivalent doses of EB and E. This was accomplished by determining thresholds for E-induced lordosis. OVX females were approximately seven times less sensitive to E than to EB. CI 628 had no significant effects on E-induced lordosis, in contrast to the complete abolition of lordosis in females treated with behaviorally equivalent EB doses. A possible mechanism to explain this differential responsiveness of EB- and E-treated females is discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/21935/1/0000342.pd

Facilitation of lordosis in ovariectomized rats by intracerebral progesterone implants

Ovariectomized female rats were estrogen-primed by subcutaneous injection and two days later were tested for sexual receptivity 6 h following bilateral implants of crystalline progesterone or cholesterol combined with a subthreshold injection of progesterone administered systemically. Cannulae were located in either the medial basal hypothalamus (MBH) or the mesencephalic reticular formation (MRF) in different groups of females.Significant facilitation of estrous behavior was induced by brain progesterone in females whose cannulae were located in the MBH. Intracerebral progesterone was not effective in females with MRF cannulae. Within the MBH the ventromedial and arcuate nuclei appeared most responsive to the estrus-facilitating actions of progesterone. The possibility that the behavioral effects of implanted progesterone were mediated by entry of hormone into the ventricular system or general circulation is considered unlikely. It is suggested that progesterone facilitates lordosis behavior via a facilitatory rather than an inhibitory effect on MBH neurons.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33988/1/0000260.pd

Sterol transporters at membrane contact sites regulate TORC1 and TORC2 signaling.

Membrane contact sites (MCSs) function to facilitate the formation of membrane domains composed of specialized lipids, proteins, and nucleic acids. In cells, membrane domains regulate membrane dynamics and biochemical and signaling pathways. We and others identified a highly conserved family of sterol transport proteins (Ltc/Lam) localized at diverse MCSs. In this study, we describe data indicating that the yeast family members Ltc1 and Ltc3/4 function at the vacuole and plasma membrane, respectively, to create membrane domains that partition upstream regulators of the TORC1 and TORC2 signaling pathways to coordinate cellular stress responses with sterol homeostasis

Sexual behavior in peripherally anosmic male hamsters

Sexually experienced and inexperienced male hamsters mated normally after they had been rendered temporarily anosmic by intranasal zinc sulfate treatment (Experiment 1), in contrast to the complete absence of sexual behavior following removal of the olfactory bulbs. The efficacy of our zinc sulfate technique was demonstrated by use of an olfactory discrimination training procedure. Hamsters lost the ability to smell both amyl acetate (Experiment 2) and the female hamster post-estrus vaginal discharge (Experiment 3) following zinc sulfate induced anosmia but at the same time retained normal sexual behavior.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33961/1/0000231.pd

Individual differences in sexual responsiveness to estrogen and progesterone in ovariectomized rats

Individual differences among 83 ovariectomized rats in behavioral responsiveness to estrogen were measured by scoring the quality of sexual receptivity induced by injections of estradiol benzoate (EB) and progesterone (P). The P dose remained constant but the quantity of EB administered was systematically reduced over successive weeks until lordosis behavior could no longer be elicited. This EB dose was considered threshold. This sequence of weekly hormone injections and receptivity tests was repeated to assess the reliability of our procedures. Animals had thresholds of either 2.0, 1.0 or 0.5 [mu]g/kg EB on both tests; the correlation between threshold values on the two tests was high (r=0.66; p<0.001). Sixty-two females were used to determine the facilitating effects of various quantities of P following EB treatment. Subgroups were tested after the E alone and again after one of 6 P doses. Zero, 20, 50 and 100 [mu]g P failed to elevate receptivity scores significantly; both 250 and 500 [mu]g P had significant facilitating effects. The results demonstrated that individual differences in EB sensitivity can be measured reliably, and a further analysis also suggests similar individual differences in P responsiveness. Our threshold determination procedures provide a useful technique for measuring the effects of various experimental manipulations on the hormone sensitivity of brain mechanisms which regulate estrous behavior.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34132/1/0000416.pd

Neonatal and two-stage olfactory bulbectomy: Effects on male hamster sexual behavior

The copulatory behavior of sexually mature male hamsters was investigated following removal of the olfactory bulbs in ways which might be expected to minimize postoperative behavioral effects. Neither two-stage bulbectomy in adults nor a one-stage operation in neonates prevented the total abolition of sexual behavior consequent to bilateral olfactory bulb removal in most of the animals. However, two bulbectomized hamsters (one, one-stage; one, two-stage) displayed an atypical persistence of mating postoperatively. Their lesions, which included total bilateral destruction of the main and accessory bulbs and damage to adjacent olfactory tissue, were histologically comparable to the lesions in two other bulbectomized hamsters (from different studies) which also copulated postoperatively. The behavior of these atypical animals supports the hypothesis that male hamsters can display normal sexual behavior in the absence of olfactory stimulation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22387/1/0000836.pd

Neurons of origin and fiber trajectory of amygdalofugal projections to the medial preoptic area in syrian hamsters

The amygdaloid neurons of origin and the trajectory of amygdaloid fibers to the medial preoptic area of the adult male Syrian hamster were identified by using horseradish peroxidase (HRP) histochemistry. After iontophoresis of HRP into the medial preoptic area, retrogradely labeled amygdaloid neurons were located in the dorsal and caudal parts of the medial amygdaloid nucleus and throughout the amygdalohippocampal area. No amygdaloid neurons were labeled after HRP applications confined to the most rostral portion of the medial preoptic area (anterior to the body of the anterior commissure). Following more caudal medial preoptic area injections (body of the anterior commissure to the suprachiasmatic nucleus) the distribution of retrogradely labeled cells in the medial amygdaloid nucleus and the amygdalohippocampal area revealed no topographic organization of the amygdalopreoptic connections. When amygdaloid neurons were labeled, the amygdalohippocampal area contained two to five times as many HRP-filled cells as the medial amygdaloid nucleus. Retrogradely transported HRP could be followed from the medial preoptic area to the amygdala through fibers in the dorsomedial quadrant of the stria terminalis. In addition, electrolytic lesions of the stria terminalis prior to iontophoresis of HRP into the medial preoptic area prevented retrograde transport to neurons in both the dorsocaudal medial amygdaloid nucleus and the amygdalohippocampal area. These results confirm earlier observations describing the location of autoradiographically labeled efferents from the medial amygdaloid nucleus to the medial preoptic area and provide new information about the restricted region within the medial amygdaloid nucleus from which these projections arise. They also suggest that, unlike the projections from the medial amygdaloid nucleus to the bed nucleus of the stria terminalis, the efferents to the medial preoptic area travel entirely in the stria terminalis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50043/1/902800106_ftp.pd

Progesterone: Examination of its postulated inhibitory actions on lordosis during the rat estrous cycle

Three experiments tested whether the inhibitory effects of progesterone could be of physiological significance in regulating the duration of behavioral estrus in female rats. In animals displaying 5 day estrous cycles, a second period of sexual receptivity, one day following the occurrence of spontaneous estrus, could be induced by exogenous hormone administration, regardless of whether the ovaries were intact or were removed during the period over which the exogenous hormones were acting. In a second experiment, acute ovariectomy at various times during the progesterone surge acted only to degrade the quality of receptive behavior subsequently observed, never to enhance it by removing a postulated inhibitory influence. In the final experiment there was some suggestion that progesterone's facilitating effect on lordosis during the later portions of spontaneous estrus were attenuated by prior exposure to ovarian secretions during the early period of behavioral estrus. Our results are consistent with the hypothesis that the duration of receptive behavior under physiological conditions is not primarily regulated by inhibitory actions of progesterone, but rather by the quantity and duration of estrogen secretions during the conditioning period.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/21689/1/0000080.pd

Effects of the antiestrogens, MER-25 and CI 628, on rat and hamster lordosis

Antiestrogens were used to test the hypothesis that estrogen exerts a "maintenance," as well as a "priming," effect on rat and hamster sexual receptivity as it apparently does for guinea pigs. MER-25 (75 or 150 mg/kg) significantly reduced rat LQ when given -2 hr or 8 hr after EB injection. MER-25 given at 34 hr (2 hr prior to P) failed to diminish rat LQ. With hamsters, MER-25 in large doses (750 mg/kg) given either at -2 hr or 34 hr reduced lordosis duration to 40% of controls, but this effect was confounded by severe illness among the MER-25 injected animals. Lower doses failed to block behavior, but still produced some toxicity. CI 628 (50 mg/kg) greatly reduced hamster lordosis duration and increased lordosis latency when given 0 hr, but not 34 hr, after EB. The results are consistent with similar previous work on rats and do not support the concept of estrogen "maintenance" in either rats or hamsters.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/21682/1/0000072.pd

Hormonal induction of behavioral estrus modified by electrical stimulation of hypothalamus

Sexual receptivity was induced by sequential injections of estrogen and progesterone in ovariectomized female rats which had bilateral, monopolar electrodes permanently implanted into either the medial preoptic area (MPOA) or the medial basal hypothalamus (MBH). Intermittent electrical stimulation of the MPOA during the first 6 hours of estrogen priming significantly reduced the intensity of estrous behavior measured 2 days later. Comparable stimulation of the MBH produced a non-significant increase in receptivity. The use of electrical stimulation to study the ways in which hormones affect central sites of action is discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34075/1/0000354.pd