PMID- 9751487
OWN - NLM
STAT- MEDLINE
DCOM- 19981008
LR  - 20131121
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 139
IP  - 10
DP  - 1998 Oct
TI  - Effects of castration and chronic steroid treatments on hypothalamic 
      gonadotropin-releasing hormone content and pituitary gonadotropins in male 
      wild-type and estrogen receptor-alpha knockout mice.
PG  - 4092-101
AB  - Testicular androgens are integral components of the hormonal feedback loops that 
      regulate circulating levels of LHbeta and FSH. The sites of feedback include 
      hypothalamic areas regulating GnRH neurons and pituitary gonadotropes. To better 
      define the roles of androgen receptor (AR), estrogen receptor-alpha (ERalpha), 
      and estrogen receptor-beta (ERbeta) in mediating feedback effects of sex steroids 
      on reproductive neuroendocrine function, we have determined the effects of 
      castration and steroid replacement therapy on hypothalamic GnRH content, 
      pituitary LHbeta and FSHbeta messenger RNA (mRNA) levels, and serum gonadotropins 
      in male wild-type (WT) and estrogen receptor-alpha knockout (ERKO) mice. 
      Hypothalami from intact WT and ERKO males contained similar amounts of GnRH, 
      whereas castration significantly reduced GnRH contents in both genotypes. 
      Replacement therapy with estradiol (E2), testosterone (T), or dihydrotestosterone 
      (DHT) restored hypothalamic GnRH content in castrated (CAST) WT mice; only the 
      androgens were effective in CAST ERKOs. Analyses of pituitary function revealed 
      that LHbeta mRNA and serum LHbeta levels in intact ERKOs were 2-fold higher than 
      those in intact WT males. Castration increased levels of LHbeta mRNA (1.5- to 
      2-fold) and serum LHbeta (4- to 5-fold) in both genotypes. Both E2 and T 
      treatments significantly suppressed LHbeta mRNA and serum LH levels in CAST WT 
      males. However, E2 was completely ineffective, and T was only partially effective 
      in suppressing these two indexes in the CAST ERKO males. DHT treatments 
      stimulated a 50% increase in LHbeta mRNA and serum LH levels in WT males, whereas 
      serum LH was significantly suppressed in DHT-treated ERKO males. Although the 
      pituitaries from intact ERKO males contained similar amounts of FSHbeta mRNA, 
      serum FSH levels were 20% higher than those in the intact WT males. Castration 
      increased FSHbeta mRNA levels only in WT males, but significantly increased serum 
      FSH levels in both genotypes. Both E2 and T treatments significantly suppressed 
      serum FSH in CAST WT males, whereas only E2 suppressed FSHbeta mRNA. DHT 
      treatments of CAST WT mice stimulated a small increase in serum FSH, but failed 
      to alter FSHbeta mRNA levels. None of the steroid treatments exerted any 
      significant effect on FSHbeta mRNA or serum FSH levels in CAST ERKOs. These data 
      suggest that hypothalamic GnRH contents can be maintained solely through AR 
      signaling pathways. However, normal regulation of gonadotrope function requires 
      aromatization of T and activation of ERalpha signaling pathways in the 
      gonadotrope. In addition, serum FSH levels in male ERKOs appear to be regulated 
      largely by nonsteroidal testicular factors such as inhibin. Finally, these data 
      suggest that hypothalamic ERbeta may not be involved in mediating the negative 
      feedback effects of T on serum LH and FSH in male mice.
FAU - Lindzey, J
AU  - Lindzey J
AD  - Receptor Biology Section, Laboratory of Reproductive and Developmental 
      Toxicology, National Institute for Environmental Health Sciences, National 
      Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
FAU - Wetsel, W C
AU  - Wetsel WC
FAU - Couse, J F
AU  - Couse JF
FAU - Stoker, T
AU  - Stoker T
FAU - Cooper, R
AU  - Cooper R
FAU - Korach, K S
AU  - Korach KS
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Gonadal Steroid Hormones)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Estrogen)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
RN  - 4TI98Z838E (Estradiol)
RN  - 9002-67-9 (Luteinizing Hormone)
RN  - 9002-68-0 (Follicle Stimulating Hormone)
SB  - IM
MH  - Animals
MH  - Castration
MH  - Estradiol/blood
MH  - Follicle Stimulating Hormone/*blood/genetics
MH  - Gonadal Steroid Hormones/*pharmacology
MH  - Gonadotropin-Releasing Hormone/*analysis
MH  - Hypothalamus/*chemistry
MH  - Luteinizing Hormone/*blood/genetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - RNA, Messenger/analysis
MH  - Receptors, Estrogen/*physiology
EDAT- 1998/09/29 00:00
MHDA- 1998/09/29 00:01
CRDT- 1998/09/29 00:00
PHST- 1998/09/29 00:00 [pubmed]
PHST- 1998/09/29 00:01 [medline]
PHST- 1998/09/29 00:00 [entrez]
AID - 10.1210/endo.139.10.6253 [doi]
PST - ppublish
SO  - Endocrinology. 1998 Oct;139(10):4092-101. doi: 10.1210/endo.139.10.6253.