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Effects of septal lesion on lordosis response induced by estradiol in middle-aged and old female rats
Neurobtolog) ofAgmg, Vol 6, pp 241-244. 1985 ©Ankho InternationalInc Prmtedm the U S A
0197-4580/85$3 00 + 00
Effects of Septal Lesion on Lordosis Response Induced by Estradiol in Middle-Aged and Old Female Rats L
R. L E E , * J O H N Y. L
Y U ? A N D M. T PENG~t2
*Department o f Physiology, Tatpet Medical College, Tatpet 105 tlnstttute o f Zoology, Academia Smtca, Tatpet ! 15 qtDepartment o f Physiology, College o f Medicine, National Tatwan University Tatpet I00, Tatwan. Repubhc o f China R e c e i v e d 22 J a n u a r y 1985 LEE, L R , J Y L YU AND M T PENG Effetts ofseptal lesion on lordosis response induced by estradtol m freddie-aged and old female rats NEUROBIOL AGING 6(3) 241-244, 1985 --Long-Evans female rats were divided mto three age groups 10 young rats (5 months of age), 7 middle-aged rats (10--13months of age) and 6 old rats (21-27 months of age) The rats were ovanectomlzed and immediately implanted subcutaneously with a sdastlc capsule filled with estradlol benzoate (E2) Lordosis response was compared m each animal before and after the septal lesion Serum E~ levels were 197+27 pg/ml (mean-+SEM), 192_+81pg/ml and 405_+83pg/ml m young, middle-aged and old rats respectively When serum E2 levels were adjusted by analysis of covanance, LQ (lordosis quotient) was 42, 36 and 61 m young, middle-aged and old rats respectively before the septal lesion and 98, 68 and 88 respectwely after the septal lesion The extent of potentiation of lordosis after the septal les~on was less m middle-aged and old rats than young rats These results md~cate that an enhanced lordosis response m aged rats is partly due to high circulating E2 levels and partly due to dlsmhlbltlon oftbe septal region on lordosis Lordosis
Middle-aged female rats
Serum estradlol level
Old female rats
Septal lesion
havlor and/or increased behavioral responsiveness to ovarian hormones has been produced m female rats by means of cortical spreadmg depression [22], lesions In the preoptic area [21], postenor hypothalamus [9], septal region [15,16] and amygdalotd [12], by olfactory bulbectomy [14] and by the anterior roof deafferentatlon [24,25]. The extrahypothalamlc mlubltory mechamsms on lordosis of forebram and amygdaiold coming through the septum [15,16] appear to exert a tomc inhibition One possibility of enhanced lordosis of old female rats is a d~smhlbmon of the central mh~bltory mechanisms on lordosis In the present study, the enhancing effect of septal lesion was compared among different age groups of female rats in order to assess any age-related difference in the inhibitory mechamsm on lordosis, so as to elucidate the mechamsm of enhanced lordosis in old female rats
E N H A N C E D lordosis response was reported m old female rats by daily reJection of estradiol [3, 17, 18] but not when using estrad~ol plus progesterone injections [17] It seems that enhanced lordosis can be induced m certain experimental condmons m old female rats In these studies, blood estradlol (E2) levels were not determmed Therefore, we do not know whether enhanced lordosis is induced by agerelated difference in the blood E2 level and/or by age-related changes m the central lordosis mechanism There are central facthtatory mechamsms and inhibitory mechanisms on lordosis, and the expression of lordosis is the balance of these two opposite mechanisms Lesions of the ventromed~al hypothalamus suppress hormonal reduction of lordosis [5, 11, 13, 20], whereas electrical stimulation or estrogen lmplantauon to the ventromedial nucleus facilitates the display of lordosis [2,19] Lesions restricted to the antenobasal hypothalamus also decrease or abohsh female sexual behavior [9,23], whereas destruction of the preoptlc area faclhtates lordotic behavior m rats [5,21] Thus, the ventromedml hypothalamus and the antenobasal hypothalamus are believed to play a faclhtatory role in mducmg lordosis On the other hand, potenUaUon of female sexual be-
METHOD Female rats of the Long-Evans strata were dwlded mto three age groups young rats (5 months of age), middle-aged rats (10-13 months of age) and old rats (21-27 months of
~Thls study was supported by National Soence Council Grant No NSC-74-0412-B002-03 The results were presented at Ist International Congress of Comparatwe Physiology and Biochemistry, Liege, Belgmm, August 27-31, 1984 2Requests for repnnts should be addressed to M T Peng, Department of Physiology, College of Medicine, Nauonal Tatwan Umverslty, No 1 Jen-m Rd, Sect 1, Teapel 100, TaJwan, Repubhc of Chma
241
242
L E E , YU A N D PENG TABLE 1 SERUM ESTRADIOL CONCENTRATION AND LORDOSIS QUOTIENT IN DIFFERENT AGE GROUPS OF RATS BEFORE AND AFTER THE SEFTAL LESION
Serum estrad~ol concentration Groups
Age month
No of rats
Young
5
10
Body weight g 267-+
7*
Before
Lordosis quotient
After pg/ml
197_+ 27
268-+
Before 17
M~ddle-aged
10-13
7
280 -+ 18
192 ± 81
194 _+ 54
Old
21-27
6
295-+ 20
405_ 83
386-- 118
42-+
After
5
98-+ 1
(42) 42 _+ 10 (36) 67_+ 5 (61)
(98) 73 -+ 7 (68) 87-+ 4 (88)
*Mean _ SEM The lordosis quotient value m the parentheses represents the value adjusted for serum estra&ol concentration by analys~s of covanance
age) The rats were mmntmned w~th free access to food and water, under a reversed hghtmg schedule of 14 hr ofhght and 10 hr darkness (hght off 11:00 hr, on 21 00 hr) All rats were ovanectom~zed and tmmedmtely implanted subcutaneously w~th a 2 5 mm long estra&ol benzoate (E2)-filled sflastac tublng (1 57 mm i d , 3 18 mm o . d , Dow Cormng) [10], using ether as anesthesm The vaginal smears were not exanuned p n o r to o v a n e c t o m y Old female rats regardless of their vaginal smear p~ctures were used, because ~t was found that lordosis responses of old rats showed no difference among rats wtth different vaginal smear pictures [17]
Abraham [1] and Hotchklss et al [8] The mtra- and mterassay coefficient of variation were 8 79% and 10 60% respectwely Benzene instead of dlethyl ether was used for E2 extratlon
Htstologt¢al Exammatton At the end of the test senes, rats were sacrificed under ether and perfused mtracranmlly with saline followed by 10% formahn The brmn was removed and fixed m 10% formahn The frozen sections o f the brmn were stained with hematoxyhn-eosm and examined microscopically to make sure of the region of the lesion
Behavior Test F w e days after the E2 tmplantatlon, lordosis behavior was tested dmly for four consecutive days Dunng the test, two sexually v~gorous males and an expenmental female were placed m a large circular Plexlglas chamber (23× 17") for 30 mm The test began at 14 00 hr and was conducted m the animal room The test area of the room was &rely dlumlhated with a red 25 watt bulb lamp directed at the wall. Male rats were habituated m the test arena for 10 mm before the test Lordosis quotient (LQ, lordosis to mount ratio× 100) of the first d a y ' s test was usually lower than LQ of the tests on later days and the stabilized high value of L Q was adopted
Septal Lesion A bdateral septal les~on was performed according to Nance et al [15] with the following coordinates. 1 4 mm antenor, 0 75 mm lateral, down 4 mm from the dura The cranial electrode was 0 75 mm stmnless steel msulated w~th Krylon, except for 0 5 mm at the t~p A 4 mA direct current was passed for 20 see with h~gh frequency lesion maker (Grass LM4) An indifferent electrode was placed on the opposite smde o f the ear
Hormone Assay Blood samples were taken from the jugular veto right after the f'mal sexual behavior test both before and after the septal lesion under a hght ether anesthesm Serum E2 concentration was measured by RIA using the modtfied procedures from
Stattsttcal Analysts Differences of body weight, serum E2 concentration and L Q among 3 age groups were evaluated by A N O V A or analysis of covanance RESULTS
Body weight of rats had a tendency to increase as age advanced, but the difference among 3 age groups was not statistically significant, F(2,20)=0 99 (Table l) The ies~ons were primarily restricted to the lateral septum The medial septum, bed nucleus of the s t n a termmahs, anterior commissure and fornlx were intact LQ and serum E2 levels m different age groups before and after the septal les~on are shown m Table 1 It shows that there was an age difference m the E2 levels, F(2,20)=3 61, p < 0 05, and LQ, F(2,20)=3 85, p < 0 05, before the septal les~on Because the magmtude o f lordosis response is sexsteroid dependent, hxgh L Q of old rats could be due to l~gh serum E2 level In order to analyze this posslbdlty, LQ was calculated by analysis of covanance to adjust the serum E2 level to be similar among 3 age groups When the serum E2 level was adjusted to the mean value of 3 age groups there was stdl an age difference m the LQ, F(2,19)=3 66, p < 0 05 Adjusted L Q s were 42, 36 and 61 respectzvely m young, middle-aged and old rats After the septal lesion, there was still an age difference m the LQ, F(2,20)=6 19, p < 0 01, and m the serum E2, F(2,20)=6 05, p < 0 01 When the serum E2 level was adjusted, there was still an age difference m the
SEPTAL LESION ON LORDOSIS IN OLD RATS
243
LQ, F(2,19)=3 8 5 , p < 0 05 Adjusted LQs were 98, 68and 88 respectively in young, middle-aged and old rats The increase of LQ after the septal lesion w~s 56, 32 and 29 respectively in young, middle-aged and old rats DISCUSSION High blood E2 levels were observed m old rats even with an implantation of the same size of E2-fiUed silastic capsule as m young rats There was no statistically significant difference in the body weight among 3 age groups, so there would be no significant difference in the blood volume among 3 age groups Thus, body weight factor would not contribute to the high blood E2 level m old rats In order to assess whether high LQ of old rats is merely due to high blood E2 level or due to other mechanisms coupled with high blood E2 level, LQ among different age groups must be compared on the base of similar blood E2 levels By analysis of covanance, LQ was adjusted for similar blood E, levels among 3 age groups Even after adjustment of blood E2 levels, LQ was higher in old rats than young rats Therefore, the enhanced lordosis in old rats can not be explained only by the Ingh serum E~ level of old rats There are inlub~tory mechanisms on lordosis m the amygdala [12], olfactory bulb [14] and forebrmn [22] and the mInbltory pathways come to the preoptic area [25] and the hypothalamus [24] through the septum [15,16] The possibility of dtsinMbltion of the minbitory mechamsm from the forebram on lordoms in old female rats was studied using effects of septal lesions on the lordosis response The extent of potentiation of lordosis after the septal lesion was less In middle-aged and old rats than young rats Tins imphes that there was dtsminbmon of lordosis from the septum m advancing age Tins would contribute to the enhanced lordosis
in old rats The criticism that middle-aged and old rats showed a higher LQ than young rats before the septal lesion and that their LQs did not easily exceed that of young rats after the septal lesion (because of a "'ceiling effect") has to be taken into consideration However, this possiblhty seems to be unlikely, because the LQ of middle-aged and old rats after the septal lesion was actually lower than that of young rats A direct approach, using subcutaneous implantation of sdastic capsules f'flled with low doges of E2, is in progress There is some discrepancy on enhanced lordosis m old female rats Enhanced lordosis was observed in ovanectomlzed old rats after dmly injections of E2 [3] but not in intact old female rats [4] Gray, et al [7] could not find enhanced lordosis m middle-aged female rats Data from our previous reports [17,18] show that old female rats can be divided into two groups from the standpoint of lordosis response to sex steroids, one group of rats showed a decreased response and the other showed a normal or even an enhanced lordosis response Enhanced lordosis was observed only m the E2 injected group [17,18], but not m the group injected with E~ plus progesterone [17] These results and the present study, taken together, mdmate that enhanced lordosis can not be observed in intact old female rats but can only be elicited m rats with high blood E~ levels coupled with dismhlbltion of lordosis Many markers of reproductive aging such as ovarian cycles lengthened or lost, smaller E.~-mduced LH surge, pulsatlle release of LH, smaller postovanectomy LH elevation, decreased negahve feedback sensitivity of E~ on LH, gha hyperactivity in the arcuate nucleus, lactotroph adenoma and prolactinemla are delayed by chronic ovanectomy or accelerated by chromc E: [6] Whether the same is true in the d~sminbmon of the central inhibitory mechanism on lordosis m aged rats remained to be evaluated
REFERENCES 1 Abraham, G E Sohd-phase radlolmmunoassayofestradlol-17 Chn Endo~rmol (OxJ) 29. 866--870, 1969 2 Barfield, R J and J J Chen Activatlonofestrous behavlorm ovanectomized rats by intracerebral implants of estradlol benzoate Endocrinology 101. 1716-1725, 1977 3 Cooper, R L Sexual receptivity in aged female rats Horm Behav 9" 321-333, 1977 4 Cooper, R L and M Linnolla Sexual behavior in aged, noncycling female rats Phvs:ol Behav 18" 573-576, 1977 5 Dorner, G , F Docke and G Hmz Homo- and hypersexuallty in rats with hypothalamm lesions Neuroendocrlnologv 4. 20-24, 1969 6 Finch, C E , L S Fehclo, C V Mobb and J F Nelson Ovarian and steroidal influence on neuroendocnne aging processes in female rodents Endocr Rev 5 467--497, 1984 7 Gray, G D , B Tennent, E R Smith and J M Davldson Lutelmzmg hormone regulation and sexual behavior in middleaged female rats Endocrinology 107: 187-194, 1980 8 Hotchklss, J , J E Atkmson and E Knobll Time course of serum estrogen and luteimzmg hormone (LH) concentrations dunng the menstrual cycle of the rhesus monkey Endo~rmology 89: 177-183, 1971 9 Law, T and W Meagher Hypothalamic lemon and sexual behavior in the female rat Science 128" 1626-1627, 1958 10 Legan, S J , G A Conn and F J Karsch Role of estrogen as initiator of dally LH surges in the ovanectomized rat Endocrinology 96" 50-56, 1975
11 Malsbury, C W , L-M Kowand D W Pfaff Effects of medial hypothalamlc lesions on the lordosis response and other behaviors in female golden hamsters Phystol Behav 19 223-237, 1977 12 Masco, D H and H F Carrer Sexual recepnvsty in female rats after lesion or stimulation in different amygdalold nuclei Phystol Behav 24: 1073--1080, 1980 13 Mathews, K and A Edwards Involvement of ventromedial and anterior hypothalamlc nuclei in the hormonal Induction of receptivity in the female rat Phystol Behav 19" 319-326, 1977 14 Moss, R L Modification of copulatory behavior in the female rat following olfactory bulb removal J Comp Physlol Psycho/ 74: 374--382, 1971 15 Nance, D M , J Shryne and R A Gorskl Septal lesions Effects on lordosis behavior and pattern of gonadotropm release Horm Behav 5: 73--81, 1974 16 Nance, D M , J Shryne and R A Gorskl Effect of septal lesion on behavioral sensitivity of female rats to gonadal hormones Horm Behav 6: 59---64, 1975 17 Peng, M T , C F Chuong and Y M Peng Lordosis response of semle female rats Neuroendocrinologv 24: 317-324, 1977 18 Peng, M T , C T Yao and W C-M Wan Dissociation between female sexual behavior and iutemtzang hormone release in old female rats Phsytol Behav 25: 633-636, 1980 19 Pfaff, D W and Y Sakuma Facilitation of the lordosis reflex of female rats from the ventromedial nucleus of the hypothalamus J Phystol (Lond) 288" 189--202, 1979
244
20 Pfaff, D W and Y Sakuma Deficit in the lordosis reflex of female rats caused by lesions m the ventromedlal nucleus of the hypothalamus Am J Phys:ol 237. R278-284, 1979 21 Powers, B and E S Valenstem Fac~htatton by medial preoptic lesions in female rats Science 175. 1003-1005, 1972 22 Ross, J W , R A Gorsl~ and C H Sawyer Effects of conical stimulation on estrous behavior m estrogen-primed ovanectormzed rats Endocr:nologv 93: 20-25, 1973 23 Stager, J J Hypothalanuc control of male and female behavior m female rats J Comp Phystol Psychol 66. 738-742, 1968
LEE, YU AND PENG
24 Yamanouchi, K and Y Arm Possible mlubitory role of the dorsal mputs to the preoptic area and hypothalamus m regularmg female sexual behavior in the female rat Brain Res 127: 296-301, 1977 25 Yamanouchi, K Inlubitory and facihtatory neural mechamsms involved m the regulation of lordosis behavior in female rats Effects of dual cuts m the preoptic area and hypothalamus Phsylo/Behav 25. 721-725, 1980
0197-4580/85$3 00 + 00
Effects of Septal Lesion on Lordosis Response Induced by Estradiol in Middle-Aged and Old Female Rats L
R. L E E , * J O H N Y. L
Y U ? A N D M. T PENG~t2
*Department o f Physiology, Tatpet Medical College, Tatpet 105 tlnstttute o f Zoology, Academia Smtca, Tatpet ! 15 qtDepartment o f Physiology, College o f Medicine, National Tatwan University Tatpet I00, Tatwan. Repubhc o f China R e c e i v e d 22 J a n u a r y 1985 LEE, L R , J Y L YU AND M T PENG Effetts ofseptal lesion on lordosis response induced by estradtol m freddie-aged and old female rats NEUROBIOL AGING 6(3) 241-244, 1985 --Long-Evans female rats were divided mto three age groups 10 young rats (5 months of age), 7 middle-aged rats (10--13months of age) and 6 old rats (21-27 months of age) The rats were ovanectomlzed and immediately implanted subcutaneously with a sdastlc capsule filled with estradlol benzoate (E2) Lordosis response was compared m each animal before and after the septal lesion Serum E~ levels were 197+27 pg/ml (mean-+SEM), 192_+81pg/ml and 405_+83pg/ml m young, middle-aged and old rats respectively When serum E2 levels were adjusted by analysis of covanance, LQ (lordosis quotient) was 42, 36 and 61 m young, middle-aged and old rats respectively before the septal lesion and 98, 68 and 88 respectwely after the septal lesion The extent of potentiation of lordosis after the septal les~on was less m middle-aged and old rats than young rats These results md~cate that an enhanced lordosis response m aged rats is partly due to high circulating E2 levels and partly due to dlsmhlbltlon oftbe septal region on lordosis Lordosis
Middle-aged female rats
Serum estradlol level
Old female rats
Septal lesion
havlor and/or increased behavioral responsiveness to ovarian hormones has been produced m female rats by means of cortical spreadmg depression [22], lesions In the preoptic area [21], postenor hypothalamus [9], septal region [15,16] and amygdalotd [12], by olfactory bulbectomy [14] and by the anterior roof deafferentatlon [24,25]. The extrahypothalamlc mlubltory mechamsms on lordosis of forebram and amygdaiold coming through the septum [15,16] appear to exert a tomc inhibition One possibility of enhanced lordosis of old female rats is a d~smhlbmon of the central mh~bltory mechanisms on lordosis In the present study, the enhancing effect of septal lesion was compared among different age groups of female rats in order to assess any age-related difference in the inhibitory mechamsm on lordosis, so as to elucidate the mechamsm of enhanced lordosis in old female rats
E N H A N C E D lordosis response was reported m old female rats by daily reJection of estradiol [3, 17, 18] but not when using estrad~ol plus progesterone injections [17] It seems that enhanced lordosis can be induced m certain experimental condmons m old female rats In these studies, blood estradlol (E2) levels were not determmed Therefore, we do not know whether enhanced lordosis is induced by agerelated difference in the blood E2 level and/or by age-related changes m the central lordosis mechanism There are central facthtatory mechamsms and inhibitory mechanisms on lordosis, and the expression of lordosis is the balance of these two opposite mechanisms Lesions of the ventromed~al hypothalamus suppress hormonal reduction of lordosis [5, 11, 13, 20], whereas electrical stimulation or estrogen lmplantauon to the ventromedial nucleus facilitates the display of lordosis [2,19] Lesions restricted to the antenobasal hypothalamus also decrease or abohsh female sexual behavior [9,23], whereas destruction of the preoptlc area faclhtates lordotic behavior m rats [5,21] Thus, the ventromedml hypothalamus and the antenobasal hypothalamus are believed to play a faclhtatory role in mducmg lordosis On the other hand, potenUaUon of female sexual be-
METHOD Female rats of the Long-Evans strata were dwlded mto three age groups young rats (5 months of age), middle-aged rats (10-13 months of age) and old rats (21-27 months of
~Thls study was supported by National Soence Council Grant No NSC-74-0412-B002-03 The results were presented at Ist International Congress of Comparatwe Physiology and Biochemistry, Liege, Belgmm, August 27-31, 1984 2Requests for repnnts should be addressed to M T Peng, Department of Physiology, College of Medicine, Nauonal Tatwan Umverslty, No 1 Jen-m Rd, Sect 1, Teapel 100, TaJwan, Repubhc of Chma
241
242
L E E , YU A N D PENG TABLE 1 SERUM ESTRADIOL CONCENTRATION AND LORDOSIS QUOTIENT IN DIFFERENT AGE GROUPS OF RATS BEFORE AND AFTER THE SEFTAL LESION
Serum estrad~ol concentration Groups
Age month
No of rats
Young
5
10
Body weight g 267-+
7*
Before
Lordosis quotient
After pg/ml
197_+ 27
268-+
Before 17
M~ddle-aged
10-13
7
280 -+ 18
192 ± 81
194 _+ 54
Old
21-27
6
295-+ 20
405_ 83
386-- 118
42-+
After
5
98-+ 1
(42) 42 _+ 10 (36) 67_+ 5 (61)
(98) 73 -+ 7 (68) 87-+ 4 (88)
*Mean _ SEM The lordosis quotient value m the parentheses represents the value adjusted for serum estra&ol concentration by analys~s of covanance
age) The rats were mmntmned w~th free access to food and water, under a reversed hghtmg schedule of 14 hr ofhght and 10 hr darkness (hght off 11:00 hr, on 21 00 hr) All rats were ovanectom~zed and tmmedmtely implanted subcutaneously w~th a 2 5 mm long estra&ol benzoate (E2)-filled sflastac tublng (1 57 mm i d , 3 18 mm o . d , Dow Cormng) [10], using ether as anesthesm The vaginal smears were not exanuned p n o r to o v a n e c t o m y Old female rats regardless of their vaginal smear p~ctures were used, because ~t was found that lordosis responses of old rats showed no difference among rats wtth different vaginal smear pictures [17]
Abraham [1] and Hotchklss et al [8] The mtra- and mterassay coefficient of variation were 8 79% and 10 60% respectwely Benzene instead of dlethyl ether was used for E2 extratlon
Htstologt¢al Exammatton At the end of the test senes, rats were sacrificed under ether and perfused mtracranmlly with saline followed by 10% formahn The brmn was removed and fixed m 10% formahn The frozen sections o f the brmn were stained with hematoxyhn-eosm and examined microscopically to make sure of the region of the lesion
Behavior Test F w e days after the E2 tmplantatlon, lordosis behavior was tested dmly for four consecutive days Dunng the test, two sexually v~gorous males and an expenmental female were placed m a large circular Plexlglas chamber (23× 17") for 30 mm The test began at 14 00 hr and was conducted m the animal room The test area of the room was &rely dlumlhated with a red 25 watt bulb lamp directed at the wall. Male rats were habituated m the test arena for 10 mm before the test Lordosis quotient (LQ, lordosis to mount ratio× 100) of the first d a y ' s test was usually lower than LQ of the tests on later days and the stabilized high value of L Q was adopted
Septal Lesion A bdateral septal les~on was performed according to Nance et al [15] with the following coordinates. 1 4 mm antenor, 0 75 mm lateral, down 4 mm from the dura The cranial electrode was 0 75 mm stmnless steel msulated w~th Krylon, except for 0 5 mm at the t~p A 4 mA direct current was passed for 20 see with h~gh frequency lesion maker (Grass LM4) An indifferent electrode was placed on the opposite smde o f the ear
Hormone Assay Blood samples were taken from the jugular veto right after the f'mal sexual behavior test both before and after the septal lesion under a hght ether anesthesm Serum E2 concentration was measured by RIA using the modtfied procedures from
Stattsttcal Analysts Differences of body weight, serum E2 concentration and L Q among 3 age groups were evaluated by A N O V A or analysis of covanance RESULTS
Body weight of rats had a tendency to increase as age advanced, but the difference among 3 age groups was not statistically significant, F(2,20)=0 99 (Table l) The ies~ons were primarily restricted to the lateral septum The medial septum, bed nucleus of the s t n a termmahs, anterior commissure and fornlx were intact LQ and serum E2 levels m different age groups before and after the septal les~on are shown m Table 1 It shows that there was an age difference m the E2 levels, F(2,20)=3 61, p < 0 05, and LQ, F(2,20)=3 85, p < 0 05, before the septal les~on Because the magmtude o f lordosis response is sexsteroid dependent, hxgh L Q of old rats could be due to l~gh serum E2 level In order to analyze this posslbdlty, LQ was calculated by analysis of covanance to adjust the serum E2 level to be similar among 3 age groups When the serum E2 level was adjusted to the mean value of 3 age groups there was stdl an age difference m the LQ, F(2,19)=3 66, p < 0 05 Adjusted L Q s were 42, 36 and 61 respectzvely m young, middle-aged and old rats After the septal lesion, there was still an age difference m the LQ, F(2,20)=6 19, p < 0 01, and m the serum E2, F(2,20)=6 05, p < 0 01 When the serum E2 level was adjusted, there was still an age difference m the
SEPTAL LESION ON LORDOSIS IN OLD RATS
243
LQ, F(2,19)=3 8 5 , p < 0 05 Adjusted LQs were 98, 68and 88 respectively in young, middle-aged and old rats The increase of LQ after the septal lesion w~s 56, 32 and 29 respectively in young, middle-aged and old rats DISCUSSION High blood E2 levels were observed m old rats even with an implantation of the same size of E2-fiUed silastic capsule as m young rats There was no statistically significant difference in the body weight among 3 age groups, so there would be no significant difference in the blood volume among 3 age groups Thus, body weight factor would not contribute to the high blood E2 level m old rats In order to assess whether high LQ of old rats is merely due to high blood E2 level or due to other mechanisms coupled with high blood E2 level, LQ among different age groups must be compared on the base of similar blood E2 levels By analysis of covanance, LQ was adjusted for similar blood E, levels among 3 age groups Even after adjustment of blood E2 levels, LQ was higher in old rats than young rats Therefore, the enhanced lordosis in old rats can not be explained only by the Ingh serum E~ level of old rats There are inlub~tory mechanisms on lordosis m the amygdala [12], olfactory bulb [14] and forebrmn [22] and the mInbltory pathways come to the preoptic area [25] and the hypothalamus [24] through the septum [15,16] The possibility of dtsinMbltion of the minbitory mechamsm from the forebram on lordoms in old female rats was studied using effects of septal lesions on the lordosis response The extent of potentiation of lordosis after the septal lesion was less In middle-aged and old rats than young rats Tins imphes that there was dtsminbmon of lordosis from the septum m advancing age Tins would contribute to the enhanced lordosis
in old rats The criticism that middle-aged and old rats showed a higher LQ than young rats before the septal lesion and that their LQs did not easily exceed that of young rats after the septal lesion (because of a "'ceiling effect") has to be taken into consideration However, this possiblhty seems to be unlikely, because the LQ of middle-aged and old rats after the septal lesion was actually lower than that of young rats A direct approach, using subcutaneous implantation of sdastic capsules f'flled with low doges of E2, is in progress There is some discrepancy on enhanced lordosis m old female rats Enhanced lordosis was observed in ovanectomlzed old rats after dmly injections of E2 [3] but not in intact old female rats [4] Gray, et al [7] could not find enhanced lordosis m middle-aged female rats Data from our previous reports [17,18] show that old female rats can be divided into two groups from the standpoint of lordosis response to sex steroids, one group of rats showed a decreased response and the other showed a normal or even an enhanced lordosis response Enhanced lordosis was observed only m the E2 injected group [17,18], but not m the group injected with E~ plus progesterone [17] These results and the present study, taken together, mdmate that enhanced lordosis can not be observed in intact old female rats but can only be elicited m rats with high blood E~ levels coupled with dismhlbltion of lordosis Many markers of reproductive aging such as ovarian cycles lengthened or lost, smaller E.~-mduced LH surge, pulsatlle release of LH, smaller postovanectomy LH elevation, decreased negahve feedback sensitivity of E~ on LH, gha hyperactivity in the arcuate nucleus, lactotroph adenoma and prolactinemla are delayed by chronic ovanectomy or accelerated by chromc E: [6] Whether the same is true in the d~sminbmon of the central inhibitory mechanism on lordosis m aged rats remained to be evaluated
REFERENCES 1 Abraham, G E Sohd-phase radlolmmunoassayofestradlol-17 Chn Endo~rmol (OxJ) 29. 866--870, 1969 2 Barfield, R J and J J Chen Activatlonofestrous behavlorm ovanectomized rats by intracerebral implants of estradlol benzoate Endocrinology 101. 1716-1725, 1977 3 Cooper, R L Sexual receptivity in aged female rats Horm Behav 9" 321-333, 1977 4 Cooper, R L and M Linnolla Sexual behavior in aged, noncycling female rats Phvs:ol Behav 18" 573-576, 1977 5 Dorner, G , F Docke and G Hmz Homo- and hypersexuallty in rats with hypothalamm lesions Neuroendocrlnologv 4. 20-24, 1969 6 Finch, C E , L S Fehclo, C V Mobb and J F Nelson Ovarian and steroidal influence on neuroendocnne aging processes in female rodents Endocr Rev 5 467--497, 1984 7 Gray, G D , B Tennent, E R Smith and J M Davldson Lutelmzmg hormone regulation and sexual behavior in middleaged female rats Endocrinology 107: 187-194, 1980 8 Hotchklss, J , J E Atkmson and E Knobll Time course of serum estrogen and luteimzmg hormone (LH) concentrations dunng the menstrual cycle of the rhesus monkey Endo~rmology 89: 177-183, 1971 9 Law, T and W Meagher Hypothalamic lemon and sexual behavior in the female rat Science 128" 1626-1627, 1958 10 Legan, S J , G A Conn and F J Karsch Role of estrogen as initiator of dally LH surges in the ovanectomized rat Endocrinology 96" 50-56, 1975
11 Malsbury, C W , L-M Kowand D W Pfaff Effects of medial hypothalamlc lesions on the lordosis response and other behaviors in female golden hamsters Phystol Behav 19 223-237, 1977 12 Masco, D H and H F Carrer Sexual recepnvsty in female rats after lesion or stimulation in different amygdalold nuclei Phystol Behav 24: 1073--1080, 1980 13 Mathews, K and A Edwards Involvement of ventromedial and anterior hypothalamlc nuclei in the hormonal Induction of receptivity in the female rat Phystol Behav 19" 319-326, 1977 14 Moss, R L Modification of copulatory behavior in the female rat following olfactory bulb removal J Comp Physlol Psycho/ 74: 374--382, 1971 15 Nance, D M , J Shryne and R A Gorskl Septal lesions Effects on lordosis behavior and pattern of gonadotropm release Horm Behav 5: 73--81, 1974 16 Nance, D M , J Shryne and R A Gorskl Effect of septal lesion on behavioral sensitivity of female rats to gonadal hormones Horm Behav 6: 59---64, 1975 17 Peng, M T , C F Chuong and Y M Peng Lordosis response of semle female rats Neuroendocrinologv 24: 317-324, 1977 18 Peng, M T , C T Yao and W C-M Wan Dissociation between female sexual behavior and iutemtzang hormone release in old female rats Phsytol Behav 25: 633-636, 1980 19 Pfaff, D W and Y Sakuma Facilitation of the lordosis reflex of female rats from the ventromedial nucleus of the hypothalamus J Phystol (Lond) 288" 189--202, 1979
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20 Pfaff, D W and Y Sakuma Deficit in the lordosis reflex of female rats caused by lesions m the ventromedlal nucleus of the hypothalamus Am J Phys:ol 237. R278-284, 1979 21 Powers, B and E S Valenstem Fac~htatton by medial preoptic lesions in female rats Science 175. 1003-1005, 1972 22 Ross, J W , R A Gorsl~ and C H Sawyer Effects of conical stimulation on estrous behavior m estrogen-primed ovanectormzed rats Endocr:nologv 93: 20-25, 1973 23 Stager, J J Hypothalanuc control of male and female behavior m female rats J Comp Phystol Psychol 66. 738-742, 1968
LEE, YU AND PENG
24 Yamanouchi, K and Y Arm Possible mlubitory role of the dorsal mputs to the preoptic area and hypothalamus m regularmg female sexual behavior in the female rat Brain Res 127: 296-301, 1977 25 Yamanouchi, K Inlubitory and facihtatory neural mechamsms involved m the regulation of lordosis behavior in female rats Effects of dual cuts m the preoptic area and hypothalamus Phsylo/Behav 25. 721-725, 1980