1396

Specialia

d a y of life r e v e a l e d v e r y s i m i l a r dissociations c o n s t a n t s (KD) of t h e r e c e p t o r - h o r m o n e c o m p l e x in b o t h groups, n a m e l y r a n g i n g b e t w e e n 4.95 a n d 5.12 • 10 -1~ M -1 in cont r o l r a t s a n d b e t w e e n 5.15 a n d 5.38 • 10 -10 M -1 i n a d r e n a l e c t o m i z e d rats. T h e d e c r e a s e in o v a r i a n g o n a d o t r o p h i n s e n s i t i v i t y a f t e r a d r e n a l e c t o m y c a n be r e s t o r e d b y glucocorticoidsl~ n . T h e q u e s t i o n arises in w h i c h w a y glucocorticoids m a y i n f l u e n c e o v a r i a n g o n a d o t r o p h i n s e n s i t i v i t y ; glucocort i c o i d s h a v e b e e n f o u n d to m o d u l a t e t h e a c t i o n of v a r i o u s h o r m o n e s o n t o t h e i r t a r g e t cells 21, 22. R e c e n t l y E n g e l a n d F r o w e i n 2~ a n d S c h m i d t k e e t al.34 p r e s e n t e d e v i d e n c e t h a t in t h e r a t t e s t i s t h i s ' p e r m i s s i v e effect' of t h e glucoc o r t i c o i d s is p o s s i b l y d u e t o a n i n h i b i t o r y effect o n t o t h e c y c l i c - A M P p h o s p h o d i e s t e r a s e , w h i c h is e n g a g e d in t h e h y d r o l y s i s of cyclic-AMP. If glucocorticoids a c t in a similar w a y in t h e o v a r i a n cells, t h e lack of glucocorticoids in a d r e n a l e c t o m i z e d p r e p u b e r t a l r a t s m a y r e s u l t in a lowered i n t r a c e l l u l a r c y c l i c - A M P level and, in c o n s e q u e n c e of this, in a r e d u c e d g o n d a l steroidogenesis. T h e i n t e r p l a y of t h e a d r e n a l s a n d t h e o v a r i e s d u r i n g f e m a l e r a t d e v e l o p m e n t is r a t h e r s h o r t ~. S e x u a l m a t u r a -

Behavioural

consequences

of v a s e c t o m y

EXPERIENTIA 33/10

t i o n is o n l y i m p a i r e d if t h e a d r e n a l e c t o m y is p e r f o r m e d before t h e 2 5 t h d a y of age, b u t e v e n in t h e s e r a t s v a g i n a l opening and ovulation occur spontaneously, although delayed. F u r t h e r m o r e , a d u l t a d r e n a l e c t o m i z e d r a t s m a i n t a i n o v u l a t o r y cycles a n d c a n r e p r o d u c e K If t h e glucocorticoids a c t in t h e o v a r i a n cells b y i n h i b i t i o n of cyclicA M P p h o s p h o d i e s t e r a s e , as s u g g e s t e d a b o v e , t h e i r a c t i o n s h o u l d b e r e s t r i c t e d w i t h r e s p e c t to d e v e l o p m e n t a l time. Cyclic-AMP phosphodiesterases have been found to exist in t h e pre- a n d p o s t p u b e r t a l o v a r y in 2 m o l e c u l a r f o r m s e x h i b i t i n g d i s t i n c t k i n e t i c p r o p e r t i e s (J. S c h m i d t k e , personal c o m m u n i c a t i o n ) . T h e q u e s t i o n is n o w u n d e r s t u d y of w h e t h e r t h e s e m o l e c u l a r f o r m s (isozymes) differ f r o m e a c h o t h e r in t h e i r i n h i b i t i o n b y glucocorticoids before a n d a f t e r t h e 2 5 t h d a y of age. 21 J. P. Jost and H. V. Rickenberg, A. Rev. Biochem. dO, 741 (1971). 22 D. Gospodarowicz, Nature 249, 123 (1974). 23 W. Engel and J. Frowein, Nature 251, 146 (1974). 24 J. Schmidtke, Th. Wienker, M. Flfigel and W. Engel, Nature 262, 593 (1976).

in the mouse

R. J. A i t k e n a n d J. C a r t e r 1

Department o/ Genetics, University o/ Edinburgh, West Mains Road, Edinburgh E H 9 3 J N (Scotland), 31 January 1977 Summary. V a s e c t o m y was f o u n d to h a v e n o i n f l u e n c e o n t h e s e x u a l a c t i v i t y of m a l e mice. T e s t i s a n d s e m i n a l vesicle w e i g h t s were s i m i l a r y n o t i n f l u e n c e d b y t h i s o p e r a t i o n a l t h o u g h a s i g n i f i c a n t i n c r e a s e in e p i d i d y m u s w e i g h t was observed. I n o r d e r t o d e m o n s t r a t e t h e a c c e p t a b i l i t y of v a s e c t o m y as a m e a n s of s t e r i l i z a t i o n , t h e influence of t h i s o p e r a t i o n o n long t e r m s e q u e l a e s u c h as a u t o - i m m u n e disease 2-4 a n d g r a n u l o m a d e v e l o p m e n t 5 as well as s e x u a l a c t i v i t y a n d libido m u s t b e e s t a b l i s h e d . W h i l e t h e r e h a s b e e n n o s h o r t age of r e s e a r c h on t h e p h y s i o l o g i c a l s t a t u s of v a s e c t o m i z e d a n i m a l s ~, ~, t h e b e h a v i o u r a l c h a n g e s i n d u c e d b y t h i s t r e a t ment have been largely neglected despite their import a n c e . R o d g e r s a n d Ziegler 7 o b s e r v e d a s l i g h t i n c r e a s e in t h e f r e q u e n c y of h u m a n i n t e r c o u r s e following v a s e c t o m y , a l t h o u g h t h e i n t e r v i e w a n d q u e s t i o n n a i r e p r o c e d u r e used in this, a n d s i m i l a r clinical studies, m a y h a v e b e e n inf l u e n c e d b y m o t i v a t e d d i s t o r t i o n s of recall a n d r e p o r t i n g b y t h e s u b j e c t s . U n f o r t u n a t e l y , few a t t e m p t s h a v e b e e n made to obtain more objective data with laboratory species. M c G l y n n a n d E r p i n o 8 c o m p a r e d v a r i o u s a s p e c t s of c o i t a l b e h a v i o u r in i n t a c t a n d v a s e c t o m i z e d rats, b u t d i d n o t i n v e s t i g a t e c o i t a l f r e q u e n c y in t h e s e a n i m a l s . I n a clinical c o n t e x t , h o w e v e r , it is t h e f r e q u e n c y r a t h e r t h a n

t h e n o r m a l i t y of c o p u l a t i o n w h i c h w o u l d seem t h e more v a l i d c r i t e r i o n of s e x u a l a c t i v i t y . A s t u d y was t h e r e f o r e d e s i g n e d to assess t h e influence of v a s e c t o m y o n c o i t a l freq u e n c y in t h e mouse. T h e m o u s e was c h o s e n for t h i s exp e r i m e n t b e c a u s e t h e p r e s e n c e of a v a g i n a l c o p u l a t i o n p l u g in t h i s species p e r m i t s t h e r e a d y i d e n t i f i c a t i o n of m a t e d females.

1 2 3 4 5 6 7 8

J. C. is grateful to the Ford Foundation for financial support. A.M. Phadke and K. Padukone, J. Reprod. Fert. 7, 163 (1964). R. Ansbacher, Fert. Steril. 22, 629 (1971). S. Shulman, E. Zappi, U. Ahmed and J. E. Davis, Contraception 5, 269 (1972). J.M. Bedford, Biol. Reprod. 14, 118 (1976). V.K. Naik, A. N. Thakur, A. R. Sheth, U. M. Joshi, S. S. Rao, D. S. Pardanani, J. K. Kulsreshtha and R. K. Handa, J. Reprod. Fert. 48, 441 (1976). D.A. Rodgers and F. J. Ziegler, Psychosom. Med. 30, 495 (1968). J.M. McGlynn and M. J. Erpino, J. Reprod. Fert. 40, 241 (1974).

Table 1. Coital frequencies (No. of females covered in each 10-day-period) observed in sham-operated and vasectomized mice Treatment

Duration of pre-operative test period (days)

Pre-operative coital frequency (-4- SE)

Duration of post-operative test period (days)

Post-operative coital frequency (-t- SE)

Number of mice

Experiment 1 Sham Vasectomized Experiment 2 Sham Vasectomized

23 23 51 51

5.61 -4- 0.52 4.78 :t: 0.52 6.58 -4- 0.64 7.09 4- 0.62

78 78 155 155

5.55 5.61 5.04 5.11

10 11 9 12

i 0.31 4- 0.35 4- 0.73 -4- 0.76

15. 10. 1977

Specialia

1397

Table 2. Mean testis, epididymus and seminal vesicle wights in sham-0perated and vasectomized mice Treatment

Mean testis weight i SE (mg)

Mean seminal vesicle + coagulating gland weight :t: SE (rag)

Experiment 1 Sham Vasectomized Experiment 2 Sham Vasectomized

103.44 -4- 5.25 94.55 -t- 3.78 102.39 i 4.31 98.16 -t- 4.79

371.33 -4- 13.82 340.80 q- 11.81 314:09 -4- 28.22 313.75 :~= 31.26

Mean epididymus weight :~ SE (rag)

44.02 *54.84 38.67 *65.59

! 1.49 4- 3.48 • 1.17 -4- 3.97

*p < 0.01.

Materials and methods. T h i s s t u d y was p e r f o r m e d u s i n g a d u l t m a l e mice of t h e r a n d o m b r e d Q strain. B i l a t e r a l vasectomy was carried out under Nembutal anaesthesia u s i n g a v e n t r a l a p p r o a c h . T h e v a s deferens was c u t bet w e e n single p r o x i m a l a n d d i s t a l l i g a t u r e s p l a c e d a p p r o x i m a t e l y 5 m m a p a r t . I n t h e s h a m o p e r a t i o n t h e v a s defr e n s was m o b i l i z e d w i t h a p a i r of forceps b u t n o t i n t e r r u p t e d . T h e a n i m a l s were r e s t e d for 2 weeks following t h e o p e r a t i o n before t h e r e c o m m e n c e m e n t of m a t i n g trials. I n o r d e r t o r e c o r d c o i t a l f r e q u e n c y t h e m a l e s were placed in s e p a r a t e cages t o g e t h e r w i t h 4 n o r m a l a d u l t females of t h e s a m e s t r a i n . T h e s e females were s u b s e q u e n t l y c h e c k e d d a i l y for t h e p r e s e n c e of v a g i n a l plugs. As soon as a n a n i m a l h a d b e e n m a t e d she was r e m o v e d f r o m t h e cage a n d r e p l a c e d b y a n o t h e r female. A t t h e e n d of t h e experim e n t t h e m a l e s were killed b y c e r v i c a l d i s l o c a t i o n a n d t h e i r testes, e p i d i d y m e s a n d s e m i n a l vesicles r e m o v e d , c l e a n e d a n d weighed. 2 e x p e r i m e n t s were p e r f o r m e d w h i c h differed o n l y in t h e d u r a t i o n of t h e pre- a n d p o s t o p e r a t i v e periods. T h e significance of t h e r e s u l t s was assessed b y t h e a n a l y s i s of v a r i a n c e .

1

~

Results and discussion. T h e coital f r e q u e n c i e s ( n u m b e r of females m a t e d in e a c h 10-day-period) o b s e r v e d in exp e r i m e n t s 1 a n d 2 are p r e s e n t e d in t a b l e 1. T h e pre- a n d p o s t - o p e r a t i v e s scores o b s e r v e d for t h e v a s e c t o m i z e d anim a l s a n d t h e p o s t - o p e r a t i v e scores r e c o r d e d for t h e s h a m o p e r a t e d a n d v a s e c t o m i z e d g r o u p s were n o t s i g n i f i c a n t l y d i f f e r e n t f r o m e a c h o t h e r . Testis a n d s e m i n a l vesicle w e i g h t s (table 2) were s i m i l a r l y n o t i n f l u e n c e d b y vasect o m y , a n d no s i g n i f i c a n t c o r r e l a t i o n was o b s e r v e d bet w e e n t e s t i s w e i g h t a n d coital f r e q u e n c y . I n c o n t r a s t , epid i d y m u s w e i g h t s h o w e d a h i g h l y s i g n i f i c a n t increase (p < 0.01) following v a s e c t o m y ( t a b l e 2), a p p a r e n t l y as t h e r e s u l t of fluid a c c u m u l a t i o n . T h e r e s u l t s o b t a i n e d in t h e s e e x p e r i m e n t s i n d i c a t e t h a t m a l e s e x u a l a c t i v i t y is n o t i n f l u e n c e d b y v a s e c t o m y , t h e r e b y c o n f i r m i n g t h e clinical d a t a . T h e m e a s u r e m e n t of coital f r e q u e n c y w o u l d seem a p a r t i c u l a r l y useful t e s t of s e x u a l a c t i v i t y in a n u m b e r of o t h e r c o n t e x t s , s u c h as assessing t h e influence of a n t i - a n d r o g e n s , o e s t r o g e n s or p r o g e s t e r o n e s on m a l e s e x u a l f u n c t i o n , a n d m a y p r o v i d e more meaningful information than the detailed analysis of coital b e h a v i o u r .

1~

varian~HCG-binding in hemlcastrated immature female/rats* J. w . S i e b e r s l a n d W. Engel2

Universitiits-Frauenhlinih, Hugstetterstrasse 55, D-7800 Freiburg, and Institut [i~r Humangenetih und Anthropologie der Universitiit, Albertstrasse 11, D-7800 Freiburg (Federal Republic o/Germany, BRD), 28 March 1977 Summary. H e m i g o n a d e c t o m y in 9-day-old f e m a l e r a t s r e s u l t s in a d r a s t i c i n c r e a s e in t h e w e i g h t a n d t h e n u m b e r of H C G - b i n d i n g sites of t h e r e m a i n i n g o v a r y d u r i n g f u r t h e r d e v e l o p m e n t . H o w e v e r , o n a p e r m g basis of o v a r i a n weight, t h e n u m b e r of H C G - r e c e p t o r s is i d e n t i c a l in h e m i c a s t r a t e d a n d c o n t r o l rats. In the adult rat after unilateral ovariectomy, the other o v a r y e n l a r g e s ( ' c o m p e n s a t o r y h y p e r t r o p h y ' ) 3-5. E v e n a f t e r r e m o v a l of one o v a r y a n d a h a l f t h e r e m a i n i n g ovarian fragment has been found to hypertrophy to the w e i g h t of o n e o v a r y in c o n t r o l rats6. T h e m o s t f a v o u r e d h y p o t h e s i s to e x p l a i n c o m p e n s a t o r y h y p e r t r o p h y is t h a t t h e t r a n s i e n t decrease in b l o o d s t e r o i d levels f r o m r e m o v a l of one o v a r y r e d u c e s t h e n e g a t i v e f e e d b a c k effect of t h e s t e r o i d s a n d t h e r e b y t r i g g e r s a n i n c r e a s e in g o n a d o t r o p h i n s e c r e t i o n of t h e p i t u i t a r y ~-n. T h i s increase causes t h e r e m a i n i n g o v a r y to i n c r e a s e in size a n d s e c r e t o r y a c t i v i t y . A c c o r d i n g l y , o e s t r a d i o l or oestriol t r e a t m e n t of t h e hemiovariectomized rat prevents the compensatory ovarian h y p e r t r o p h y 9, 12. This work was supported in part by the Deutsche Forschungsgemeinsehaft (SFB 46). Purified HCG was a gift of Schering AG, Berlin-West. We thank Mrs Margarete Lindig for assistance and Mrs Ursula Frigewski for secretarial help,

1

Address reprint request to JWS, Universit~ts-Frauenklinik, Hugstetterstrasse 55, D-7800 Freiburg, Federal Republic of Germany, /3RD. 2 Present address: Institut fiir Humangenetik der Universit~it, Nikolausberger Weg 5a, D-3400 G6ttingen, BRD. 3 J. Slonaker, Am. J. Physiol. 81,620 (1927). 4 C. Heller, E. Heller and E. Sevringhaus, Endocrinology 30, 309 I1942). 5 N.B. Schwartz, Biol. Reprod. 10, 236 (1974). 6 R.D. Peppler, Experientia 31, 243 (1975). 7 B. Benson, S. Sorrentino and J. S. Evans, Endocrinology 8J, 369 (1969). 8 B . E . Howland and K. R. Skinner, J. Reprod. Fert. 32, 501 (1973). 9 V.D. Ramirez and C. H. Sawyer, Endoerinol0gy 94, 475 (1974). 10 R. Welschen and J. Dullaart, J. Endocr. 63, 421 (1974). 11 R . J . Remstein and S. Sorrentino, Jr, J. Repro& Fert. 48, 237 (1976). 12 D. Petersen, R. Edgren and R. Jones, Am. Zool. 2, 547 (1962).

Behavioural consequences of vasectomy in the mouse.

1396 Specialia d a y of life r e v e a l e d v e r y s i m i l a r dissociations c o n s t a n t s (KD) of t h e r e c e p t o r - h o r m o n e c o...
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